MedWorm: Virotherapy

Semireplication-competent vesicular stomatitis virus as a novel platform for oncolytic virotherapy

Journal of Molecular Medicine — Fri, 27 Jan 2012 17:53:02 +0100

In conclusion, srVSV is a promising platform for virotherapeutic approaches and also for VSV-based vector vaccines, combining improved safety with an increased coding capacity for therapeutic transgenes, potentially allowing for multipronged approaches. Content Type Journal ArticleCategory Original ArticlePages 1-12DOI 10.1007/s00109-012-0863-6Authors Alexander Muik, Georg-Speyer-Haus, 60596 Frankfurt am Main, GermanyCatherine Dold, Institute for Virology, Innsbruck Medical University, Fritz-Pregl-Str. 3, A-6020 Innsbruck, AustriaYvonne Geiß, Georg-Speyer-Haus, 60596 Frankfurt am Main, GermanyAndreas Volk, Georg-Speyer-Haus, 60596 Frankfurt am Main, GermanyMarina Werbizki, Georg-Speyer-Haus, 60596 Frankfurt am Main, GermanyUrsula Dietrich, Georg-Speyer-Haus, 60596 Frankfurt am Mai...

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Response to Intra-Arterial Oncolytic Virotherapy with the Herpes Virus NV1020 Evaluated by [18F]Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography

Human Gene Therapy — Mon, 16 Jan 2012 16:52:53 +0100

Human Gene Therapy Jan 2012, Vol. 23, No. 1: 91-97. (Source: Human Gene Therapy)

A Transductionally Retargeted Adenoviral Vector for Virotherapy of Her2/neu-Expressing Prostate Cancer

Human Gene Therapy — Mon, 16 Jan 2012 16:52:42 +0100

Human Gene Therapy Jan 2012, Vol. 23, No. 1: 70-82. (Source: Human Gene Therapy)

Functional hyper-IL-6 from vaccinia virus-colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy

Journal of Translational Medicine — Wed, 11 Jan 2012 05:00:00 +0100

Conclusion: Therefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects. (Source: Journal of Translational Medicine)

Oncolytic virotherapy in veterinary medicine: current status and future prospects for canine patients

Journal of Translational Medicine — Wed, 04 Jan 2012 05:00:00 +0100

Oncolytic viruses refer to those that are able to eliminate malignancies by direct targeting and lysis of cancer cells, leaving non-cancerous tissues unharmed. Several oncolytic viruses including adenovirus strains, canine distemper virus and vaccinia virus strains have been used for canine cancer therapy in preclinical studies. However, in contrast to human studies, clinical trials with oncolytic viruses for canine cancer patients have not been reported. An 'ideal' virus has yet to be identified. This review is focused on the prospective use of oncolytic viruses in the treatment of canine tumors - a knowledge that will undoubtedly contribute to the development of oncolytic viral agents for canine cancer therapy in the future. (Source: Journal of Translational Medicine)

Newcastle Disease Virus: a Promising Agent for Tumor Immunotherapy.

Clinical and Experimental Pharmacology and Physiology — Wed, 28 Dec 2011 05:00:00 +0100

Authors: Zhao L, Liu H Abstract Malignant tumors are a major cause of mortality in humans. Currently employed therapeutic regimens have not much improved survival rates of patients suffering from malignant tumors because of their limited efficacy and side effects. A novel therapeutic approach employs the use of the Newcastle Disease Virus (NDV) that represents an attractive new tool for tumor immunotherapy. The aim of the present review is to highlight the mechanisms and advances that are likely to have considerable impact on NDV virotherapy. There exists significant evidence regarding the oncolytic effects of NDV suggesting its potential use in the treatment of various tumors. Furthermore, clinical trials have suggested that several NDV strains have the potential for cancer viroth...

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Virotherapy - cancer targeted pharmacology.

Drug Discovery Today — Fri, 16 Dec 2011 05:00:00 +0100

Authors: Tedcastle A, Cawood R, Di Y, Fisher K, Seymour L Abstract Building on their success in vaccination, many groups are now exploring the use of viruses as anticancer agents. In general, viral therapeutics provide the possibility to express anticancer proteins directly at the tumour site, decreasing exposure to normal tissue during delivery and maximising therapeutic index. Some viruses are also 'oncolytic', either naturally or by design, and these agents function to kill cancer cells selectively before spreading to infect adjacent cells and repeat the process. This whole field of cancer 'virotherapy' is moving forward rapidly at the moment, with notable clinical successes demonstrated with a range of oncolytic agents developed as directly oncolytic and also as oncolytic cance...

Oncolytic Measles Virus Retargeting by Ligand Display

Springer protocols feed by Infectious Diseases — Mon, 28 Nov 2011 05:00:00 +0100

Despite significant advances in recent years, treatment of metastatic malignancies remains a significant challenge. There is an urgent need for development of novel therapeutic approaches. Virotherapy approaches have considerable potential, and among them measles virus (MV) vaccine strains have emerged as a promising oncolytic platform. Retargeted MV strains deriving from the Edmonston vaccine lineage (MV-Edm) have shown comparable antitumor efficacy to unmodified strains against receptor expressing tumor cells with improved therapeutic index. Here, we describe the construction, rescue, amplification, and titration of fully retargeted MV-Edm derivatives displaying tumor specific receptor binding ligands on the viral surface in combination with H protein CD46 and SLAM entry ablating mutatio...

Chemovirotherapy for head and neck squamous cell carcinoma with EGFR-targeted and CD/UPRT-armed oncolytic measles virus

Cancer Gene Therapy — Fri, 11 Nov 2011 05:00:00 +0100

Chemovirotherapy for head and neck squamous cell carcinoma with EGFR-targeted and CD/UPRT-armed oncolytic measles virus Cancer Gene Therapy advance online publication, November 11, 2011. doi:10.1038/cgt.2011.75 Authors: K Zaoui, S Bossow, C Grossardt, M F Leber, C Springfeld, P K Plinkert, C von Kalle & G Ungerechts (Source: Cancer Gene Therapy)

Oncolytic virotherapy of glioma: what does it need to make it work?

Future Virology — Fri, 04 Nov 2011 12:16:02 +0100

Future Virology , November 2011, Vol. 6, No. 11, Pages 1289-1297. (Source: Future Virology)

Response to Intra-Arterial Oncolytic Virotherapy with the Herpes Virus NV1020 Evaluated by [18F]Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography

Human Gene Therapy — Fri, 14 Oct 2011 19:46:40 +0100

Human Gene Therapy , Vol. 0, No. 0. (Source: Human Gene Therapy)

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Cytolytic replication of echoviruses in colon cancer cell lines

Virology Journal — Fri, 14 Oct 2011 04:00:00 +0100

Conclusions: We have found that echovirus 12, 17 and 26 have potential as oncolytic agents against colon cancer, by comparing the cytolytic capacity of five low-pathogenic echoviruses in six colon cancer cell lines and in artificial tumors. (Source: Virology Journal)

A Transductionally Retargeted Adenoviral Vector for Virotherapy of Her2/neu-Expressing Prostate Cancer

Human Gene Therapy — Thu, 13 Oct 2011 03:07:22 +0100

Human Gene Therapy , Vol. 0, No. 0. (Source: Human Gene Therapy)

Bacterial glucuronidase as general marker for oncolytic virotherapy or other biological therapies

Journal of Translational Medicine — Tue, 11 Oct 2011 04:00:00 +0100

Conclusion: GusA therefore has the potential to be used as a general marker in the preclinical and clinical evaluation of (novel) biological therapies as well as being useful for the detection of rare cells such as circulating tumor cells. (Source: Journal of Translational Medicine)

Replication efficiency of oncolytic vaccinia virus in cell cultures prognosticates the virulence and antitumor efficacy in mice

Journal of Translational Medicine — Tue, 27 Sep 2011 04:00:00 +0100

Conclusions: These data demonstrated that insertion of VACV promoter-driven transcriptional units into the viral genome for the purpose of insertional mutagenesis did modulate the efficiency of virus replication together with antitumor efficacy as well as virulence. Replication efficiency of oncolytic VACV in cell cultures can predict the virulence and therapeutic efficacy in nude mice. These findings may be essential for rational design of safe and potent VACV strains for vaccination and virotherapy of cancer in humans and animals. (Source: Journal of Translational Medicine)

Effect of ultrasound on herpes simplex virus infection in cell culture

Virology Journal — Thu, 22 Sep 2011 04:00:00 +0100

Conclusion: These results indicate that ultrasound promotes the entry of oncolytic HSV-1 into cells. It may be useful to enhance the efficiency of HSV-1 infection in oncolytic virotherapy. (Source: Virology Journal)

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Modeling of tumor growth undergoing virotherapy

Computers in Biology and Medicine — Tue, 20 Sep 2011 06:05:30 +0100

Abstract: Tumor growth models subject to virotherapy treatment are analyzed and compared in this paper. Tumor growth conditions are obtained for each model type based on the virus infection rate and immune suppressive drug delivery. Equilibrium conditions resulted into quadratic functions for which the tumor radius remained constant during virotherapy. An irrigation tumor model for virotherapy treatment was also proposed. This model consists of irrigation layers distributed radially along the tumor and attached to a common blood circulation compartment. The irrigation model has similar dynamic and steady state characteristics to the diffusion model, which has been supported by experimental results. The irrigation model considers the immune system cell generation and consumption outside the...

Dynamics of melanoma tumor therapy with vesicular stomatitis virus: explaining the variability in outcomes using mathematical modeling

Gene Therapy — Thu, 15 Sep 2011 04:00:00 +0100

Authors: D M Rommelfanger, C P Offord, J Dev, Z Bajzer, R G Vile & D Dingli (Source: Gene Therapy)

Cancer: Tumour-fighting virus homes in

Nature — Tue, 30 Aug 2011 23:00:00 +0100

Authors: Evanthia Galanis An early clinical trial demonstrates the delivery and replication of a cancer-killing virus in metastasized tumour tissue. These promising results could provide a foundation for systemic virotherapy for patients with cancer. See Letter p.99 (Source: Nature)

Characterization of herpes simplex virus 1 strains as platforms for the development of oncolytic viruses against liver cancer

Liver International — Sat, 27 Aug 2011 16:05:23 +0100

ConclusionsThe syncytial H6‐Luc virus has a strong oncolytic potential on human HCC xenografts and could be the basis for potent OV. (Source: Liver International)

Virotherapy induces massive infiltration of neutrophils in a subset of tumors defined by a strong endogenous interferon response activity

Cancer Gene Therapy — Thu, 25 Aug 2011 23:00:00 +0100

Authors: X Fu, L Tao, A Rivera, H Xu & X Zhang (Source: Cancer Gene Therapy)

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Cancer targeting Gene-Viro-Therapy specific for liver cancer by {alpha}-fetoprotein-controlled oncolytic adenovirus expression of SOCS3 and IL-24.

Acta Biochimica et Biophysica Sinica — Wed, 10 Aug 2011 23:00:00 +0100

Authors: Cao X, Wei R, Liu X, Zeng Y, Huang H, Ding M, Zhang K, Liu XY Abstract The combination of gene therapy and virotherapy for cancer treatment has received close attention and has become a trend in the field of cancer biotherapy. A strategy called 'Cancer Targeting Gene-Viro-Therapy' (CTGVT) or 'Gene Armed Oncolytic Viral Therapy' (GAOVT) has been proposed, in which an antitumor gene is inserted into an oncolytic viral vector. In our previous study, a dual-regulated oncolytic adenovirus with enhanced safety for normal cells and strict liver cancer-targeting ability, designated Ad•enAFP•E1A•E1B (Δ55) (briefly Ad•enAFP•D55), was successfully constructed. In the current work, interleukin-24 (IL-24) and suppressor of cytokine signaling 3 (SOCS3) genes were packaged int...

Oncolytic virotherapy of breast cancer.

Gynecologic Oncology — Thu, 14 Jul 2011 23:00:00 +0100

Authors: Hartkopf AD, Fehm T, Wallwiener D, Lauer UM The use of replication competent viruses that selectively target and destroy cancer cells has rapidly evolved over the past decade and numerous innovative oncolytic viruses have been created. Many of these promising anti-cancer agents have recently entered into clinical trials (including those on breast cancer) and demonstrated encouraging safety and efficacy. Virotherapeutic strategies are thus of considerable interest to combat breast cancer in both (i) the primary disease situation in which relapse should be avoided as good as possible and (ii) in the metastatic situation which remains incurable to date. Here, we summarize data from preclinical and clinical trials using oncolytic virotherapy to treat breast cancer. This includes s...

Oncolytic HSV-1 Virotherapy: Clinical Experience and Opportunities for Progress.

Herpes — Thu, 07 Jul 2011 23:00:00 +0100

Authors: Kaur B, Chiocca EA, Cripe TP Oncolytic virotherapy with mutants derived from Herpes simplex virus (HSV) type 1 exhibit significant antitumor effects in preclinical models. Several mutants have now been tested in clinical trials for a variety of cancer types, and all have been found to be safe. While there have been hints of antitumor efficacy with prolonged survival in some cases compared with historical controls, dramatic responses have been elusive. We review the clinical experience Publish: 1 June 2011ed to date and discuss some of the biologic factors that may be limiting for virus infection and spread, as well as new strategies currently under development to enhance antitumor efficacy. PMID: 21740359 [PubMed - as supplied by publisher] (Source: Herpes)

Oncolytic Viruses for Induction, of Anti-Tumor Immunity.

Herpes — Thu, 07 Jul 2011 23:00:00 +0100

Authors: Tong AW, Senzer N, Cerullo V, Templeton NS, Hemminki A, Nemunaitis J Oncolytic virotherapy is an evolving but, as yet, unrealized treatment option for cancer. This approach harnesses the cancer-restricted replicative activity of engineered viruses to achieve tumor cell kill. Tumors that are resistant to chemotherapy or radiotherapy can be susceptible to viral oncolysis because of distinct cell kill mechanisms. There is now compelling evidence that collateral induction of anti-tumor immune responses contributes substantially to viral anti-tumor activities. In addition to the expected anti-viral immune clearance, the "danger" signal created by virus-infected cells can generate immune co-stimulation known to override immune suppression and reverse tolerance within the tumor micro...

Fusogenic Oncolytic Herpes Simplex Viruses as a Potent and Personalized Cancer Vaccine.

Herpes — Thu, 07 Jul 2011 23:00:00 +0100

This article also describes the approaches to enhance the antitumor immunity of oncolytic HSVs, and in particular, the key role played by integrating membrane-fusion activity into these viruses. Additionally, this article reviews the potential effect of certain chemotherapeutic agents (e.g. cyclophosphamide) in boosting antitumor immunity induced by oncolytic HSV, and the mechanisms behind it. In summary, all the preclinical and clinical data have suggested that HSV-based oncolytic virotherapies could likely be developed as a new generation of cancer vaccines for the treatment of solid tumors. PMID: 21740353 [PubMed - as supplied by publisher] (Source: Herpes)

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Synergistic Interaction of Telomerase-Specific Oncolytic Virotherapy and Chemotherapeutic Agents for Human Cancer.

Current Pharmaceutical Biotechnology — Thu, 07 Jul 2011 23:00:00 +0100

This article reviews synergistic interaction of virotherapy and chemotherapy, and illustrates the potential application for the treatment of human cancer. PMID: 21740362 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Biotechnology)

Strategy of Cancer Targeting Gene-Viro-Therapy (CTGVT) - A Trend in Both Cancer Gene Therapy and Cancer Virotherapy.

Current Pharmaceutical Biotechnology — Thu, 07 Jul 2011 23:00:00 +0100

Authors: Liu XY, Li HG, Yang DQ, Gu JF Cancer Targeting Gene-Viro-Therapy (CTGVT) and Gene Armed Oncolytic Virus Therapy (GAOVT) both are identical by inserting an antitumor gene into an oncolytic virus. This approach has gradually become a hot topic in cancer therapy, because that CTGVT (GAOVT) has much higher antitumor than that of either gene therapy alone or oncolytic virotherapy alone. We proposed the CTGVT strategy in 1999-2001, insisted it as a long term systematic approach to be examined over 10 years and have Publish: 1 June 2011ed 58 SCI papers some in good Journals. The CD gene armed oncolytic adenovirus therapy (GAOVT) for cancer treatment with potent antitumor effect was also named in our laboratory in 2003. Several modifications to CTGVT will be carried out by our group a...

Bugs and Drugs: Oncolytic Virotherapy in Combination with Chemotherapy.

Current Pharmaceutical Biotechnology — Thu, 07 Jul 2011 23:00:00 +0100

Authors: Wennier ST, Liu J, McFadden G Single agent therapies are rarely successful in treating cancer, particularly at metastatic or end stages, and survival rates with monotherapies alone are generally poor. The combination of multiple therapies to treat cancer has already driven significant improvements in the standard of care treatments for many types of cancers. The first combination treatments exploited for cancer therapy involved the use of several cytotoxic chemotherapy agents. Later, with the development of more targeted agents, the use of novel, less toxic drugs, in combination with the more classic cytotoxic drugs has proven advantageous for certain cancer types. Recently, the combination of oncolytic virotherapy with chemotherapy has shown that the use of these two therapie...

A viral strategy to ambush tumors

Nature Medicine — Wed, 06 Jul 2011 23:00:00 +0100

Authors: Christopher Alvarez-Breckenridge & E Antonio Chiocca A new combinatorial approach harnesses the power of immuno- and virotherapy in a vesicular stomatitis virus (VSV) vector carrying a cDNA library that expresses normal human prostate antigens, thus providing proof of principle that this vaccine can induce prostate tumor rejection in mice (pages 854–859). This strategy might bypass many of the issues associated with conventional cancer immuno- or virotherapy. (Source: Nature Medicine)

A novel fusogenic herpes simplex virus for oncolytic virotherapy of squamous cell carcinoma

Virology Journal — Thu, 09 Jun 2011 23:00:00 +0100

Conclusion: These results indicate that novel oncolytic HSV-1 vectors can be produced with the genetic background of the oncolytic HSV-1 HF, and that RH2 is deficient in gamma 34.5 genes and shows extensive cytopathic effects in oral SCC cells. RH2 may be useful in oncolytic virotherapy for oral SCC. (Source: Virology Journal)

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A novel fusogenic herpes simplex virus for oncolytic virotherapy of squamous cell carcinoma.

Herpes — Thu, 09 Jun 2011 23:00:00 +0100

CONCLUSION: These results indicate that novel oncolytic HSV-1 vectors can be produced with the genetic background of the oncolytic HSV-1 HF, and that RH2 is deficient in gamma 34.5 genes and shows extensive cytopathic effects in oral SCC cells. RH2 may be useful in oncolytic virotherapy for oral SCC. PMID: 21663640 [PubMed - as supplied by publisher] (Source: Herpes)

Myxoma virus combined with rapamycin treatment enhances adoptive T cell therapy for murine melanoma brain tumors

Cancer Immunology, Immunotherapy — Wed, 08 Jun 2011 15:44:34 +0100

Abstract Adoptive transfer of tumor-specific T cells has shown some success for treating metastatic melanoma. We evaluated a novel strategy to improve adoptive therapy by administering both T cells and oncolytic myxoma virus to mice with syngeneic B16.SIY melanoma brain tumors. Adoptive transfer of activated CD8+ 2C T cells that recognize SIY peptide doubled survival time, but SIY-negative tumors recurred. Myxoma virus killed B16.SIY cells in vitro, and intratumoral injection of virus led to selective and transient infection of the tumor. Virus treatment recruited innate immune cells to the tumor and induced IFNβ production in the brain, resulting in limited oncolytic effects in vivo. To counter this, we evaluated the safety and efficacy of co-administering 2C T cells, myx...

A novel molecular therapy using bioengineered adenovirus for human gastrointestinal cancer.

Acta Med Okayama — Tue, 31 May 2011 23:00:00 +0100

Authors: Fujiwara T Replication-selective tumor-specific viruses constitute a novel approach for treatment of neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Human telomerase is highly active in more than 85ｵ of primary cancers, regardless of their tissue origins, and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. We constructed an attenuated adenovirus 5 vector (Telomelysin, OBP-301), in which the hTERT promoter element drives expression of E1 genes. Since only tumor cells that express telomerase activity would activate this promoter, the hTERT proximal promoter would allow for preferential expression of viral genes in tumor cells, leading...

Recent advances in oncolytic virus design

Clinical and Translational Oncology — Thu, 21 Apr 2011 05:57:42 +0100

Abstract The cytolytic properties of viruses can be used to treat cancer. Replication of certain viruses is favoured in cancer cells, whereas others can be modified to obtain tumour specificity. This approach has evolved to become a new discipline called virotherapy. In addition, these replication-competent (oncolytic) viruses can be adapted as vectors for cancer gene therapy. The “armed” viruses show a double mechanism of action: direct destruction of cancer cells as a consequence of the lytic viral cycle, in combination with the effect of the therapeutic gene incorporated in the viral genome. Current trends in the field include strategies to increase the oncolytic potency of existing viruses; the evaluation of new candidates; the search for synergistic effects betwee...

Oncolytic Virotherapy: Combining First-Rate Science with an Unmet Clinical Need

Human Gene Therapy — Tue, 12 Apr 2011 19:10:37 +0100

Human Gene Therapy Apr 2011, Vol. 22, No. 4: 387-388. (Source: Human Gene Therapy)

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Activating Systemic T-Cell Immunity Against Self Tumor Antigens to Support Oncolytic Virotherapy with Vesicular Stomatitis Virus

Human Gene Therapy — Mon, 11 Apr 2011 14:31:10 +0100

Human Gene Therapy , Vol. 0, No. 0. (Source: Human Gene Therapy)

Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus

Journal of Translational Medicine — Wed, 30 Mar 2011 23:00:00 +0100

This study aimed to determine if insertion of the human sodium iodide symporter (hNIS) cDNA as a marker for noninvasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, GLV-1h153. Methods: GLV-1h153 was modified from parental vaccinia virus GLV-1h68 to carry hNIS via homologous recombination. GLV-1h153 was tested against human pancreatic cancer cell line PANC-1 for replication via viral plaque assays and flow cytometry. Expression and transportation of hNIS in infected cells was evaluated using Westernblot and immunofluorescence. Intracellular uptake of radioiodide was assessed using radiouptake assays. Viral cytotoxicity and tumor growth of treated PANC-1 tumor xenografts in nude mice was also determined. Finally, tumor radiouptake in xenog...

Oncolytic vesicular stomatitis virus administered by isolated limb perfusion suppresses osteosarcoma growth.

Cell Research — Wed, 30 Mar 2011 06:00:38 +0100

Authors: Kubo T, Shimose S, Matsuo T, Fujimori J, Sakaguchi T, Yamaki M, Shinozaki K, Woo SL, Ochi M A significant limitation to oncolytic virotherapy in vivo is the lack of a clinically relevant means of delivering the virus. We evaluated the oncolytic activity of vesicular stomatitis virus (VSV) in human osteosarcoma cells and explored isolated limb perfusion (ILP) as a novel oncolytic virus delivery system to extremity sarcoma in immune-competent rats. Human and rat osteosarcoma cells transduced with rVSV-lacZ uniformly expressed β-gal. VSV was fully capable of replicating its RNA genome in all osteosarcoma cell lines, and efficiently killed them in time- and dose-dependent manners, whereas normal bone marrow stromal cells were refractory to the virus. VSV delivered by ILP inhibite...

Clinical development directions in oncolytic viral therapy

Cancer Gene Therapy — Fri, 25 Mar 2011 00:00:00 +0100

Authors: R M Eager & J Nemunaitis (Source: Cancer Gene Therapy)

Translational research in oncolytic measles virotherapy: early discoveries and future steps

Future Microbiology — Wed, 02 Mar 2011 16:47:23 +0100

Future Microbiology , February 2011, Vol. 6, No. 2, Pages 125-128. (Source: Future Microbiology)

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Viral-mediated oncolysis is the most critical factor in the late-phase of the tumor regression process upon vaccinia virus infection

BMC Cancer — Mon, 14 Feb 2011 00:00:00 +0100

Conclusions: Taken together, these results indicate that VACV-mediated oncolysis is the primary mechanism of tumor shrinkage in the late regression phase. Neither the destruction of the tumor vasculature nor the massive VACV-mediated intratumoral inflammation were a prerequisite for tumor regression. We propose that approaches to enhance viral replication and spread within the tumor microenvironment should improve therapeutical outcome. (Source: BMC Cancer)

Oncolytic Targeting of Androgen-sensitive Prostate Tumor by the Respiratory Syncytial Virus (RSV): Consequences of Deficient Interferon-dependent Antiviral Defense

BioMed Central — Fri, 28 Jan 2011 00:00:00 +0100

Conclusions: We demonstrated that RSV is potentially a useful therapeutic tool in the treatment of androgen-sensitive and androgen-independent prostate cancer. Moreover, impaired IFN-mediated antiviral response is the likely cause of higher viral burden and resulting oncolysis of androgen-sensitive prostate cancer cells. (Source: BioMed Central)

CXCR4 Tumor Specific Promoter Restricts Oncolysis To Pancreatic Cancer Cell Lines That Overexpress CXCR4

Journal of Surgical Research — Wed, 19 Jan 2011 20:26:50 +0100

Conclusions: The novel Ad5/3-CXCR4 CRAd was highly efficient and specific in infecting and lysing human pancreatic cancer cells. Further development and testing of this novel construct should be considered for potential therapy against pancreatic cancer. (Source: Journal of Surgical Research)

The Novel Modified Oncolytic Adenovirus Ad5/3-CXCR4 Exhibits Potent Antitumor Effect And Limited Host Toxicity Against Xenograft Human Pancreatic Cancers In SCID Mice

Journal of Surgical Research — Wed, 19 Jan 2011 20:26:50 +0100

Conclusions: The novel Ad5/3-CXCR4 adenoviruses not only exhibited a potent antitumor effect against xenograft human pancreatic cancers in SCID mice, but also demonstrated no observable host toxicity. Thus, Ad5/3-CXCR4 serves as a promising candidate for clinical treatment of pancreatic adenocarcinoma. (Source: Journal of Surgical Research)

Oncolysis of malignant human melanoma tumors by Coxsackieviruses A13, A15 and A18

Virology Journal — Tue, 18 Jan 2011 00:00:00 +0100

Many RNA viruses are displaying great promise in the field of oncolytic virotherapy. Previously, we reported that the picornavirus Coxsackievirus A21 (CVA21) possessed potent oncolytic activity against cultured malignant melanoma cells and melanoma xenografts in mice. In the present study, we demonstrate that three additional Group A Coxsackieviruses; Coxsackievirus A13 (CVA13), Coxsackievirus A15 (CVA15) and Coxsackievirus A18 (CVA18), also have similar oncolytic activity against malignant melanoma. Each of the viruses grew quickly to high titers in cancer cells expressing ICAM 1 and intratumoral injection of preformed subcutaneous SK Mel-28 xenografts in mice with CVA13, CVA15 and CVA18 resulted in significant tumor volume reduction.As preexisting immunity could potentially hinder oncoly...

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Vaccinia virus GLV-1h237 carrying a Walker A motif mutation of mouse Cdc6 protein enhances human breast tumor therapy in mouse xenografts.

International Journal of Oncology — Tue, 18 Jan 2011 00:00:00 +0100

Authors: Hofmann E, Grummt F, Szalay AA Recently it was shown that recombinant vaccinia virus GLV-1h68 is a promising tool for treating different type of cancers in animal models. The goal of the present study was to enhance the oncolytic potential of GLV-1h68 without decreasing its safety. A derivative of GLV-1h68 containing the gene for a Walker A motif mutant of the essential cell cycle protein Cdc6, GLV-1h237, was engineered. The characteristics of GLV-1h237 and its efficiency in treating human breast cancer GI-101A cells were compared with that of GLV-1h236 (carrying the wild-type gene for Cdc6), GLV-1h71 (a derivative of GLV-1h68) and GLV-1h68, respectively. RT-PCR and immunoblot analyses revealed that Cdc6 is efficiently overexpressed in GLV-1h237-infected GI-101A cells. GLV-1h2...

The emerging role of viruses in the treatment of solid tumours

Cancer Treatment Reviews — Thu, 13 Jan 2011 05:00:00 +0100

Abstract: There is increasing optimism for the use of non-pathogenic viruses in the treatment of many cancers. Initial interest in oncolytic virotherapy was based on the observation of an occasional clinical resolution of a lymphoma after a systemic viral infection. In many cancers, by comparison with normal tissues, the competency of the cellular anti-viral mechanism is impaired, thus creating an exploitable difference between the tumour and normal cells, as an unimpeded viral proliferation in cancer cells is eventually cytocidal. In addition to their oncolytic capability, these particular viruses may be engineered to facilitate gene delivery to tumour cells to produce therapeutic effects such as cytokine secretion and anti -tumour immune responses prior to the eventual cytolysis. There i...

Efficient virotherapy for osteosarcoma by telomerase-specific oncolytic adenovirus

Journal of Cancer Research and Clinical Oncology — Thu, 30 Dec 2010 18:03:31 +0100

Conclusions This study indicated that virotherapy with Telomelysin may provide a promising strategy for the treatment of human osteosarcoma. Content Type Journal ArticleDOI 10.1007/s00432-010-0969-6Authors Guidong Li, Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510 JapanHiroyuki Kawashima, Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510 JapanAkira Ogose, Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510 JapanTakashi Ariizumi, Division of Orthopedic Surgery, Graduate Schoo...

Treatment of patient tumor-derived colon cancer xenografts by a TRAIL gene-armed oncolytic adenovirus

Cancer Gene Therapy — Fri, 24 Dec 2010 00:00:00 +0100

Authors: W Zhou, H Zhu, W Chen, X Hu, X Pang, J Zhang, X Huang, B Fang & C He (Source: Cancer Gene Therapy)

Enhanced oncolysis mediated by Coxsackievirus A21 in combination with doxorubicin hydrochloride

Investigational New Drugs — Mon, 20 Dec 2010 18:09:03 +0100

Summary Virotherapy is an emerging strategy for the treatment of cancer that utilizes both replication-competent and genetically modified viruses to selectively kill tumor cells. We have previously shown that Coxsackievirus A21 (CVA21), a common-cold producing enterovirus, is an effective oncolytic agent against human melanoma, prostate, and breast cancer xenografts in vivo. CVA21 specifically targets and lytically infects susceptible cells expressing the CVA21 cellular receptors, intercellular adhesion molecule-1 (ICAM-1) and decay-accelerating factor (DAF). Herein, the efficacy of CVA21 administered in combination with doxorubicin hydrochloride as a new therapeutic regimen for cancer was investigated. Flow cytometric analysis demonstrated that the human breast, colorecta...

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Oncolytic vesicular stomatitis virus administered by isolated limb perfusion suppresses osteosarcoma growth

Journal of Orthopaedic Research — Mon, 20 Dec 2010 00:10:21 +0100

AbstractA significant limitation to oncolytic virotherapy in vivo is the lack of a clinically relevant means of delivering the virus. We evaluated the oncolytic activity of vesicular stomatitis virus (VSV) in human osteosarcoma cells and explored isolated limb perfusion (ILP) as a novel oncolytic virus delivery system to extremity sarcoma in immune‐competent rats. Human and rat osteosarcoma cells transduced with rVSV‐lacZ uniformly expressed β‐gal. VSV was fully capable of replicating its RNA genome in all osteosarcoma cell lines, and efficiently killed them in time‐ and dose‐dependent manners, whereas normal bone marrow stromal cells were refractory to the virus. VSV delivered by ILP inhibited growth of osteosarcoma xenografts more potently than that injected intravenously and ...

Oncolytic virotherapy of gynecologic malignancies.

Gynecologic Oncology — Tue, 07 Dec 2010 00:00:00 +0100

CONCLUSIONS: While gaining more and more insight into the underlying molecular mechanisms of OVs, virotherapy represents an appealing approach to fight gynecologic malignancies. PMID: 21145097 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)

Oncolytic poliovirus therapy and immunization with poliovirus-infected cell lysate induces potent antitumor immunity against neuroblastoma in vivo.

International Journal of Oncology — Fri, 03 Dec 2010 05:58:02 +0100

Authors: Toyoda H, Wimmer E, Cello J In a previous study, we demonstrated that neuroblastoma subcutaneously implanted in immuno-competent mice is eliminated by intratumoral administration of neuroattenuated poliovirus (PV). Our results also suggested that the in vivo destruction of neuroblastoma cells by virotherapy lead to a robust antitumor immune response. In this work, splenocytes harvested from neuroblastoma-bearing animals treated with neuroattenuated PV exhibited significantly higher lytic activity against tumor target cells than did those from splenocytes derived from control mice. In vitro T-cell depletion experiments indicated that CD8+ T cells were essential for the cytotoxic antitumor activity of splenocytes. Moreover, adoptive transfer of splenocytes obtained from mice cur...

Rapamycin enhances the activity of oncolytic herpes simplex virus against tumor cells that are resistant to virus replication

International Journal of Cancer — Thu, 02 Dec 2010 00:00:00 +0100

AbstractOncolytic herpes simplex virus (HSV) is currently in phase III clinical trials for development as a novel therapeutic agent against a broad range of human tumors. Although results have been promising, clinical outcome is likely to be compromised by intrinsic and acquired resistance to HSV replication, leading us to test agents that may overcome this obstacle. We found that, despite showing no effect on HSV replication in tumor cells fully permissive to the virus growth, the mTOR inhibitor rapamycin dramatically increased the yield and dissemination of oncolytic HSVs in semipermissive tumor cells. Similar results were obtained in tumor‐bearing mice. Co‐administration of rapamycin with an HSV‐derived oncolytic virus either blocked or reversed the growth of tumor xenografts esta...

YB‐1 dependent virotherapy in combination with temozolomide as a multimodal therapy approach to eradicate malignant glioma

International Journal of Cancer — Thu, 18 Nov 2010 02:22:37 +0100

AbstractThe human Y‐box binding protein 1 (YB‐1) is known to be a promising target for cancer therapy. We have demonstrated that YB‐1 plays an important role in the adenoviral life cycle by regulating the adenoviral E2‐gene expression. Thus, we studied the oncolytic effect of the recombinant adenovirus Ad‐Delo3‐RGD, in which the transactivation domain CR3 of the E1A protein is ablated to enable viral replication only in YB‐1 positive cancer cells. In vitro Southern Blot analysis and cytopathic effect assays demonstrate high anti‐glioma potency, which was significantly increased in combination with temozolomide (TMZ), daunorubicin, and cisplatin. Since vascular endothelial growth factor (VEGF) is thought to promote the hypervascular phenotype of primary, malignant brain tumo...

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Telomerase-Dependent Oncolytic Adenovirus Sensitizes Human Cancer Cells to Ionizing Radiation via Inhibition of DNA Repair Machinery

Cancer Research — Sun, 14 Nov 2010 00:00:00 +0100

The inability to repair DNA double-strand breaks (DSB) leads to radiosensitization, such that ionizing radiation combined with molecular inhibition of cellular DSB processing may greatly affect treatment of human cancer. As a variety of viral products interact with the DNA repair machinery, oncolytic virotherapy may improve the therapeutic window of conventional radiotherapy. Here, we describe the mechanistic basis for synergy of irradiation and OBP-301 (Telomelysin), an attenuated type-5 adenovirus with oncolytic potency that contains the human telomerase reverse transcriptase promoter to regulate viral replication. OBP-301 infection led to E1B55kDa viral protein expression that degraded the complex formed by Mre11, Rad50, and NBS1, which senses DSBs. Subsequently, the phosphorylation of ...

CD20-targeted measles virus shows high oncolytic specificity in clinical samples from lymphoma patients independent of prior rituximab therapy

Gene Therapy — Thu, 11 Nov 2010 00:00:00 +0100

Authors: K-C Yaiw, T S Miest, M Frenzke, M Timm, P B Johnston & R Cattaneo (Source: Gene Therapy)

RIG-I Helicase-Independent Pathway in Sendai Virus-Activated Dendritic Cells Is Critical for Preventing Lung Metastasis of AT6.3 Prostate Cancer.

Neoplasia — Mon, 01 Nov 2010 00:00:00 +0100

In this study, therefore, we investigated the efficacy of vaccinating DCs activated by fusion gene-deleted nontransmissible rSeV on a rat model of lung metastasis using a highly malignant subline of Dunning R-3327 prostate cancer, AT6.3. rSeV/dF-green fluorescent protein (GFP)-activated bone marrow-derived DCs (rSeV/dF-GFP-DC), consistent with results previously observed in murine DCs. Vaccination of rSeV/dF-GFP-DC was highly effective at preventing lung metastasis after intravenous loading of R-3327 tumor cells, compared with the effects observed with immature DCs or lipopolysaccharide-activated DCs. Interestingly, neither CTL activity nor DC trafficking showed any apparent difference among groups. Notably, rSeV/dF-DCs expressing a dominant-negative mutant of retinoic acid-inducible gene ...

A Phase I Study of a Tropism-Modified Conditionally Replicative Adenovirus for Recurrent Malignant Gynecologic Diseases.

Clinical Cancer Research — Mon, 25 Oct 2010 23:00:00 +0100

CONCLUSIONS: This study, the first to evaluate an infectivity-enhanced CRAd in human cancer, shows the feasibility, safety, potential antitumor response, and biological activity of this approach in ovarian cancer. Further evaluation of infectivity enhanced virotherapy approaches for malignant gynecologic diseases is warranted. Clin Cancer Res; 16(21); 5277-87. ©2010 AACR. PMID: 20978148 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Carrier cell-based delivery of replication-competent HSV-1 mutants enhances antitumor effect for ovarian cancer

Cancer Gene Therapy — Thu, 30 Sep 2010 23:00:00 +0100

Authors: S Fujiwara, A Nawa, C Luo, M Kamakura, F Goshima, C Kondo, T Kiyono, F Kikkawa & Y Nishiyama (Source: Cancer Gene Therapy)

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Antitumoural immunity by virus-mediated immunogenic apoptosis inhibits metastatic growth of hepatocellular carcinoma

Gut — Fri, 10 Sep 2010 15:45:23 +0100

Conclusion Proteasome inhibition during virotherapy disrupts the UPR, leading to enhanced ER stress-induced apoptosis, improved local oncolysis and antitumoural immunity. The results suggest that combining intratumoural virotherapy with adjuvant systemic therapies, which specifically support the function of the virotherapy as an antitumoural vaccine, is a promising immunotherapeutic strategy against HCC. (Source: Gut)

Enhanced tumor therapy using vaccinia virus strain GLV-1h68 in combination with a β-galactosidase-activatable prodrug seco-analog of duocarmycin SA

Cancer Gene Therapy — Thu, 09 Sep 2010 23:00:00 +0100

Enhanced tumor therapy using vaccinia virus strain GLV-1h68 in combination with a β-galactosidase-activatable prodrug seco-analog of duocarmycin SA Cancer Gene Therapy advance online publication, September 10, 2010. doi:10.1038/cgt.2010.49 Authors: C M Seubert, J Stritzker, M Hess, U Donat, J B Sturm, N Chen, J M von Hof, B Krewer, L F Tietze, I Gentschev & A A Szalay (Source: Cancer Gene Therapy)

Arming a replicating adenovirus with osteoprotegerin reduces the tumor burden in a murine model of osteolytic bone metastases of breast cancer

Cancer Gene Therapy — Thu, 26 Aug 2010 23:00:00 +0100

Authors: J J Cody, A A Rivera, G R Lyons, S W Yang, M Wang, D B Sarver, D Wang, K S Selander, H-C Kuo, S Meleth, X Feng, G P Siegall & J T Douglas (Source: Cancer Gene Therapy)

Glioma stem cells as a target for treatment

Targeted Oncology — Wed, 25 Aug 2010 06:13:39 +0100

Abstract Glioma cells with stem cell-like properties represent a minor subfraction of the total tumor cell population. These cells are highly chemo- and radioresistent and are held responsible for the inevitable recurrence of malignant gliomas. This review summarizes current strategies for targeting putative glioma stem cells. Target definition approaches comprise extrapolation and adaptation of therapies from general oncology, target identification by correlative molecular genetic analyses, and dedicated target discovery research. Targeting strategies include inhibition of tumor-specific signaling pathways, enhancement of tumor cell differentiation, radiosensitization, indirect targeting of the tumor stem cell niche, oncolytic virotherapy, and adhesion molecule blockade. ...

Design of virotherapy for effective tumor treatment

Current Opinion in Molecular Therapeutics — Wed, 28 Jul 2010 23:00:00 +0100

No description available (Source: Current Opinion in Molecular Therapeutics)

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Complete regression of human malignant mesothelioma xenografts following local injection of midkine promoter-driven oncolytic adenovirus

The Journal of Gene Medicine — Wed, 14 Jul 2010 23:00:00 +0100

Malignant mesothelioma is a highly aggressive tumor with poor prognosis. We hypothesized that the tumor-specific midkine (Mdk) promoter could confer transcriptional targeting to oncolytic adenoviruses for effective treatment of malignant mesothelioma.We analysed Mdk expression by quantitative reverse transcription-polymerase chain reaction in six human mesothelioma cell lines, and tested Mdk promoter activity by luciferase reporter assay. On the basis of these data, we constructed a replication-selective oncolytic adenovirus designated AdMdk-E1-iresTK. This virus contains a Mdk promoter-driven adenoviral E1 gene and herpes simplex virus-thymidine kinase (TK) suicide gene and cytomagalovirus promoter-driven enhanced green fluorescent protein marker gene. Selectivity of viral replication and...

A fully replication-competent adenovirus vector with enhanced oncolytic properties

Cancer Gene Therapy — Thu, 01 Jul 2010 23:00:00 +0100

Authors: K Toth, M Kuppuswamy, E V Shashkova, J F Spencer & W S M Wold (Source: Cancer Gene Therapy)

Three Families Honored at Mesothelioma Symposium

Asbestos and Mesothelioma News — Mon, 21 Jun 2010 16:53:52 +0100

During the International Symposium on Malignant Mesothelioma, which was recently held on June 11th, the Bendix family, the Ruble family and the Sterling family were honored by the Mesothelioma Applied Research Foundation (MARF) for their contributions to mesothelioma research. The three families had funded three important research projects through MARF’s research program, giving the foundation the necessary funds to search for a cure. Ken Bendix and his family donated $100,000 for a grant that intends to develop a new virotherapy method to identify and treat peritoneal mesothelioma. Ken and his family funded what is now known as the Ken Bendix Research Grant before his passing in December 2009. The grant was awarded to Dr. J. Andrea McCart of the Toronto General Research Institute. The c...

VEGF blockade decreases the tumor uptake of systemic oncolytic herpes virus but enhances therapeutic efficacy when given after virotherapy

Gene Therapy — Wed, 26 May 2010 23:00:00 +0100

Authors: F K Eshun, M A Currier, R A Gillespie, J L Fitzpatrick, W H Baird & T P Cripe (Source: Gene Therapy)

Potent anti-tumor activity of telomerase-dependent and HSV-1TK armed oncolytic adenovirus for non-small cell lung cancer in vitro and in vivo

Journal of Experimental and Clinical Cancer Research — Wed, 19 May 2010 23:00:00 +0100

Conclusions: The results from this study showed that Ad.hTERT-E1A-TK could be a potent but safe anti-tumor strategy for NSCLC biotherapy. (Source: Journal of Experimental and Clinical Cancer Research)

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A probasin promoter, conditionally replicating adenovirus that expresses the sodium iodide symporter (NIS) for radiovirotherapy of prostate cancer

Gene Therapy — Wed, 28 Apr 2010 23:00:00 +0100

Authors: M A Trujillo, M J Oneal, S McDonough, R Qin & J C Morris (Source: Gene Therapy)

Oncolytic measles viruses encoding interferon β and the thyroidal sodium iodide symporter gene for mesothelioma virotherapy

Cancer Gene Therapy — Thu, 08 Apr 2010 23:00:00 +0100

Oncolytic measles viruses encoding interferon β and the thyroidal sodium iodide symporter gene for mesothelioma virotherapy Cancer Gene Therapy advance online publication, April 9, 2010. doi:10.1038/cgt.2010.10 Authors: H Li, K-W Peng, D Dingli, R A Kratzke & S J Russell (Source: Cancer Gene Therapy)

Combinatorial therapy allows viruses to destroy tumors

ScienceDaily Headlines — Sat, 03 Apr 2010 09:00:00 +0100

For several years, researchers have been developing a new approach to treating cancer that uses viruses to infect and kill cancer cells while leaving normal cells unharmed. New research indicates that this approach, which is known as oncolytic virotherapy, can be combined with a standard clinical therapy to provide substantial regression and cure of tumors in mice, leading to the suggestion that this combinatorial approach could be of tremendous benefit in the clinic. (Source: ScienceDaily Headlines)

Viruses Destroy Tumors In Combinatorial Therapy

Health News from Medical News Today — Sat, 03 Apr 2010 07:00:00 +0100

For several years, researchers have been developing a new approach to treating cancer that uses viruses to infect and kill cancer cells while leaving normal cells unharmed. Recent data have indicated that this approach, which is known as oncolytic virotherapy, has potential. Now, Richard Vile and colleagues, at the Mayo Clinic, Rochester, have found that this approach can be combined with a standard clinical therapy to provide substantial regression and cure of tumors in mice, leading them to suggest that this combinatorial approach could be of tremendous benefit in the clinic... (Source: Health News from Medical News Today)

Antiangiogenic cancer therapy combined with oncolytic virotherapy leads to regression of established tumors in mice

Kidney Cancer Association — Fri, 02 Apr 2010 14:45:21 +0100

Cancer gene/virus therapy will not achieve its potential until vectors can be delivered systemically to metastatic disease.04/03/2010 (Source: Kidney Cancer Association)

Regression of Human Prostate Tumors and Metastases in Nude Mice following Treatment with the Recombinant Oncolytic Vaccinia Virus GLV-1h68

Journal of Biomedicine and Biotechnology — Thu, 01 Apr 2010 15:24:48 +0100

Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In the current study, we analyzed the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 against two human prostate cancer cell lines DU-145 and PC-3 in cell culture and in tumor xenograft models. By viral proliferation assays and cell survival tests, we demonstrated that GLV-1h68 was able to infect, replicate in, and lyse these prostate cancer cells in culture. In DU-145 and PC-3 tumor xenograft models, a single intravenous injection with GLV-1h68 resulted in a significant reduction of primary tumor size. In addition, the GLV-1h68-infection led to strong inflammatory and oncolytic effects resulting in drastic reduction of regional lymph nodes with PC-3 metastases. ...

Combinatorial therapy allows viruses to destroy tumors

EurekAlert! - Cancer — Thu, 01 Apr 2010 04:00:00 +0100

(Journal of Clinical Investigation) For several years, researchers have been developing a new approach to treating cancer that uses viruses to infect and kill cancer cells while leaving normal cells unharmed. New research indicates that this approach, which is known as oncolytic virotherapy, can be combined with a standard clinical therapy to provide substantial regression and cure of tumors in mice, leading to the suggestion that this combinatorial approach could be of tremendous benefit in the clinic. (Source: EurekAlert! - Cancer)

Adenovirus retargeting to surface expressed antigens on oral mucosa

The Journal of Gene Medicine — Sun, 28 Mar 2010 23:00:00 +0100

Head and neck squamous cell carcinomas develop in preneoplastic mucosal fields that can extend over several centimeters in diameter. Most of these fields are microscopically recognized as dysplasias. These fields are often not adequately treated and might cause local relapse. Previous investigations demonstrated that mouthwash therapy with oncolytic adenoviruses appears to be a good option for the treatment of these fields, although, at present, with limited efficacy.Immunohistochemistry on normal and preneoplastic mucosa was applied to determine the expression levels of the coxsackie adenoviral receptor (CAR) and a few surface antigens that might allow retargeting: Ly-6D, CD44v6 and K928. Monoclonal antibodies directed against these surface antigens were used for retargeting of adenovirus...

United virus: The oncolytic tag-team against cancer!

Cytokine and Growth Factor Reviews — Mon, 15 Mar 2010 00:00:00 +0100

Abstract: There is an urgent need for innovative therapeutic strategies to treat aggressive metastatic cancers that are incurable with standard therapeutic approaches. Novel treatment strategies like oncolytic virotherapy have led, in some cases, to impressive effects on disease progression in human trials, suggesting that approval of an oncolytic virus therapeutic is on the horizon. While combinations of oncolytic viruses with small molecules are already being tested and have shown promise, we propose that even greater therapeutic synergies could be achieved through rational design of complementary virus therapeutics. In this review, we discuss rational chemical and biological combination strategies to enhance oncolytic virotherapy highlighting the promising combination of vaccinia and ve...

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Combining oncolytic virotherapy and tumour vaccination

Cytokine and Growth Factor Reviews — Fri, 12 Mar 2010 00:00:00 +0100

Abstract: The interactions between the immune system, a malignant tumour and an oncolytic virus are complex and poorly understood. For oncolytic viruses to become successful therapeutics we need to better understand these interactions and identify strategies to take advantage of defects in the innate immune response within tumours and avoid cellular anti-viral responses while capitalizing on anti-tumoural immunity. In this review we will discuss the evidence for the induction of tumour-specific immune responses by oncolytic viruses as well as by cancer vaccines. We will then describe some of the barriers to successful cancer immunotherapy, and finally we will outline a strategy for enhancing anti-tumoural immunity while reducing anti-viral immunity by combining tumour vaccination with onco...

Oncolytic herpes simplex virus armed with xenogeneic homologue of prostatic acid phosphatase enhances antitumor efficacy in prostate cancer

Gene Therapy — Thu, 11 Mar 2010 00:00:00 +0100

Authors: P Castelo-Branco, B J Passer, J S Buhrman, S Antoszczyk, M Marinelli, C Zaupa, S D Rabkin & R L Martuza (Source: Gene Therapy)

Investigators At University Of Chicago, Brain Tumor Center Have Published New Data On Cancer Gene Therapy

Cancercompass News: Other Cancer — Thu, 11 Mar 2010 00:00:00 +0100

A report, 'Virotherapy against malignant glioma stem cells,' is newly published data in Cancer Letters. Glioblastoma multiforme, the most common primary intracranial malignancy, is associated with very poor outcome despite advances in surgical techniques and chemo-and radiation therapy. Many novel treatment modalities are being investigated with varying amount of success, researchers in the United States report. (Source: Cancercompass News: Other Cancer)

Clinical trials with oncolytic reovirus: Moving beyond phase I into combinations with standard therapeutics

Cytokine and Growth Factor Reviews — Thu, 11 Mar 2010 00:00:00 +0100

Abstract: It is time for those working on oncolytic viruses to take stock of the status of the field. We now have at our disposal an array of potential therapeutic agents, and are beginning to conduct early-phase clinical trials in patients with relapsed/metastatic cancers. By drawing on lessons learned during the development of other biological therapies, such as monoclonal antibodies and targeted small molecule inhibitors, we are now in a position to chart the course of the next wave of trials that will go beyond the phase I studies of safety and feasibility. In this article we review our approach to the development of oncolytic viruses as cancer therapeutics. In doing so, we emphasise the fact that this process is modular and involves multiple iterative steps between the laboratory and ...

Enhanced anti-tumor activity by the combination of a conditionally replicating adenovirus mediated interleukin-24 and dacarbazine against melanoma cells via induction of apoptosis

Cancer Letters — Tue, 02 Mar 2010 00:00:00 +0100

In this study, we hypothesized that a combination of ZD55-IL-24-mediated gene virotherapy and chemotherapy using DTIC would produce an increased cytotoxicity against human melanoma cells in comparison with these agents alone. Our results showed that the combination of ZD55-IL-24 and DTIC significantly enhanced the anti-tumor activity by more effectively inducing apoptosis in melanoma cells than either agent used alone without any overlapping toxicity against normal cells. This additive or synergistic effect of ZD55-IL-24 in combination with DTIC in killing human malignant melanoma cells implies a promising novel approach for melanoma therapy. (Source: Cancer Letters)

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TRAIL gene-armed oncolytic poxvirus and oxaliplatin can work synergistically against colorectal cancer

Gene Therapy — Thu, 25 Feb 2010 00:00:00 +0100

Authors: M F Ziauddin, Z S Guo, M E O'Malley, F Austin, P J Popovic, M A Kavanagh, J Li, M Sathaiah, P Thirunavukarasu, B Fang, Y J Lee & D L Bartlett (Source: Gene Therapy)

Medical application of herpes simplex virus

Journal of Dermatological Science — Thu, 28 Jan 2010 14:12:48 +0100

Abstract: Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are important human pathogens that cause a variety of diseases from mild skin diseases such as herpes labialis and herpes genitalis to life-threatening diseases such as herpes encephalitis and neonatal herpes. A number of studies have elucidated the roles of this virus in viral replication and pathogenicity, the regulation of gene expression, interaction with the host cell and immune evasion from the host system. This research has allowed the development of potential therapeutic agents and vectors for human diseases. This review focuses on the basic functions and roles of HSV gene products and reviews the current knowledge of medical applications of genetically engineered HSV mutants using different strategies. These major HS...

Potent anti-tumor effects of a dual specific oncolytic adenovirus expressing apoptin in vitro and in vivo

Molecular Cancer — Wed, 20 Jan 2010 00:00:00 +0100

Conclusions: These data further reinforce the previously research showing that an adenovirus expressing Apoptin is more effective and advocate the potential applications of Ad-hTERT-E1a-Apoptin in the treatment of neoplastic diseases in future clinical trials. (Source: Molecular Cancer)

Parvovirus H1 selectively induces cytotoxic effects on human neuroblastoma cells

International Journal of Cancer — Tue, 19 Jan 2010 00:00:00 +0100

Despite multimodal therapeutic concepts, advanced localized and high-risk neuroblastoma remains a therapeutic challenge with a long-term survival rate below 50%. Consequently, new modalities for the treatment of neuroblastoma, e.g., oncolytic virotherapy are urgently required. H-1PV is a rodent parvovirus devoid of relevant pathogenic effects in infected adult animals. In contrast, the virus has oncolytic properties and is particularly cytotoxic for transformed or tumor-derived cells of various species including cells of human origin. Here, a preclinical in vitro assessment of the application of oncolytic H-1PV for the treatment of neuroblastoma cells was performed. Infection efficiency, viral replication and lytic activity of H-1PV were analyzed in 11 neuroblastoma cell lines with differe...

Myxoma Virus Virotherapy for Glioma in Immunocompetent Animal Models: Optimizing Administration Routes and Synergy with Rapamycin

Cancer Research — Thu, 14 Jan 2010 05:08:21 +0100

Tractable improvements are reported for an oncolytic viral therapy being developed for brain cancer, a largely intractable disease where more effective therapies are badly needed. (Source: Cancer Research)

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Myxoma Virus Virotherapy for Glioma in Immunocompetent Animal Models: Optimizing Administration Routes and Synergy with Rapamycin.

Cell Research — Tue, 12 Jan 2010 00:00:00 +0100

Authors: Lun X, Alain T, Zemp FJ, Zhou H, Rahman MM, Hamilton MG, McFadden G, Bell J, Senger DL, Forsyth PA Oncolytic myxoma virus (MYXV) is being developed as a novel virotherapeutic against human brain cancer and has promising activity against human brain tumor models in immunocompromised hosts. Because an intact immune system could reduce its efficacy, the purpose of this study was to evaluate the oncolytic potential of MYXV in immunocompetent racine glioma models. Here, we report that MYXV infects and kills all racine cell glioma lines and that its effects are enhanced by rapamycin. Intratumoral administration of MYXV with rapamycin improved viral replication in the tumor and significantly prolonged host survival. Similarly, coadministration via a method of convection-enhanced deli...

Oncolytic virotherapy reaches adolescence

Pediatric Blood and Cancer — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Pediatric Blood and Cancer)

Adenovirus-mediated cancer gene therapy and virotherapy (Review).

International Journal of Molecular Medicine — Sat, 05 Dec 2009 03:59:11 +0100

Authors: Fukazawa T, Matsuoka J, Yamatsuji T, Maeda Y, Durbin ML, Naomoto Y Gene therapy and virotherapy are among the approaches currently used to treat malignant tumors. Gene therapy and virotherapy use a specific therapeutic gene that causes death in cancer cells. In early attempts at gene therapy, therapeutic genes were driven by ubiquitous promoters such as the CMV promoter, which induce non-specific toxicity to normal cells and tissues in addition to the cancer cells. Recently, novel cancer- and/or tissue-specific promoter systems have been developed to target cancer cells but not normal cells including stem cells. In this review, we describe cancer and/or tissue-specific gene therapy systems for the treatment of cancer. In particular, we will discuss three systems for gene thera...

Targeting Gene-ViroTherapy for prostate cancer by DD3-driven oncolytic virus-harboring interleukin-24 gene

International Journal of Cancer — Mon, 30 Nov 2009 00:00:00 +0100

In this study, we constructed an oncolytic adenovirus Ad.DD3-E1A by using the minimal DD3 promoter to replace the native viral promoter of E1A gene. In addition, Ad.DD3-E1A was armed with therapeutic gene IL-24 to enhance its antitumor activity. The resulting adenovirus, Ad.DD3-E1A-IL-24, demonstrated PCa specificity and excellent antitumor effect. Further analyses on its antitumor mechanism revealed that it has the capacity to induce apoptosis in PCa cells and inhibit angiogenesis. These results suggest that Ad.DD3-E1A-IL-24 is a promising antitumor agent that may be able to be used in the future as a treatment for PCa. (Source: International Journal of Cancer)

Mesenchymal Stem Cell Carriers Protect Oncolytic Measles Viruses from Antibody Neutralization in an Orthotopic Ovarian Cancer Therapy Model.

Clinical Cancer Research — Tue, 24 Nov 2009 00:00:00 +0100

CONCLUSIONS: MSC should be used as carriers of MV for intraperitoneal virotherapy in measles-immune ovarian cancer patients. (Clin Cancer Res 2009;15(23):7246-55). PMID: 19934299 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

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Demonstration of anti-tumor activity of oncolytic measles virus strains in a malignant pleural effusion breast cancer model

Breast Cancer Research and Treatment — Thu, 05 Nov 2009 19:04:00 +0100

Abstract Breast cancer is the second leading cause of malignant effusions in cancer patients. Pleural effusion indicates incurable disease with limited palliative treatment options and poor outcome. Here, we demonstrate the therapeutic efficacy of measles virus (MV) vaccine strain derivative against malignant pleural effusion in an MDA-MB-231 xenograft model of advanced breast cancer. Both systemic intravenous (i.v.) and intrapleural (t.t.) administered virus caused massive infection and syncytia formation in the pleural tumor deposits. Intrapleural administration of 1.5 × 106 plaque-forming units (PFU) total dose of MV significantly improved median survival by approximately 80% compared to the control animal group. Furthermore, we tested human dendritic cells as...

Newcastle disease virus as an oncolytic agent.

Indian J Med Res — Sun, 01 Nov 2009 00:00:00 +0100

Authors: Ravindra PV, Tiwari AK, Sharma B, Chauhan RS Cancer is a major cause of deaths in humans. Though there has been significant progress in cancer therapy, the limited efficacy and toxicities of current chemo- and radiotherapies have provided an impetus for the search of new therapeutics. A therapeutic approach, which uses viruses for the treatment of cancer termed, oncolytic virotherapy has recently emerged. Newcastle disease virus (NDV) is one such virus with an inherent oncolytic property. NDV causes a highly infectious disease in poultry worldwide. In humans it is reported to have oncolytic and immuno-stimulatory effects. It specifically replicates in tumour cells while sparing normal cells and cause oncolysis. For many years different strains of the NDV have been investigated...

Targeting a Mimotope Vaccine to Activating Fc{gamma} Receptors Empowers Dendritic Cells to Prime Specific CD8+ T Cell Responses in Tumor-Bearing Mice.

Journal of Immunology — Tue, 20 Oct 2009 23:00:00 +0100

Authors: Gil M, Bieniasz M, Wierzbicki A, Bambach BJ, Rokita H, Kozbor D A major challenge for inducing antitumor immune responses with native or modified tumor/self-Ags in tumor-bearing hosts relates to achieving efficient uptake and processing by dendritic cells (DCs) to activate immune effector cells and limit the generation of regulatory T cell activity. We analyzed the ability of therapeutic DC vaccines expressing a CD166 cross-reactive mimotope of the GD2 ganglioside, 47-LDA, to selectively expand adoptively transferred, tumor-specific T cells in NXS2 neuroblastoma tumor-bearing syngeneic mice. Before the adoptive cell transfer and DC vaccination, the tumor-bearing mice were lymphodepleted by nonmyeloablative total body irradiation or a myeloablative regimen that required bone ma...

Oncolytic virotherapy for oral squamous cell carcinoma using replication-competent viruses

Oral Oncology — Thu, 15 Oct 2009 00:00:00 +0100

Summary: Oncolytic virotherapy utilizes viruses that can selectively destroy cancer cells without harming normal tissues. Clinical trials of oncolytic viruses show that most oncolytic agents are well tolerated and safe. The virotherapeutic agents currently in use have limited potency when administered alone; however, combination therapy using virotherapeutic agents and conventional anticancer agents, such as chemotherapeutics, radiation, and gene therapy, exhibits encouraging levels of efficacy. Advances in recombinant DNA technology have allowed the development of viruses that are tumor-selective and armed with transgenes, increasing the application potential and efficacy of this novel anticancer therapy. Here, we review the development of oncolytic viruses and the clinical trials of onco...

Expression of IFN-{beta} Enhances Both Efficacy and Safety of Oncolytic Vesicular Stomatitis Virus for Therapy of Mesothelioma

Cancer Research — Thu, 01 Oct 2009 18:26:05 +0100

Our preclinical and clinical trials using a replication-defective adenoviral vector expressing IFN-β have shown promising results for the treatment of malignant mesothelioma. Based on the hypotheses that a replication-competent vesicular stomatitis virus (VSV) oncolytic vector would transduce more tumor cells in vivo, that coexpression of the immunostimulatory IFN-β gene would enhance the immune-based effector mechanisms associated both with regression of mesotheliomas and with VSV-mediated virotherapy, and that virus-derived IFN-β would add further safety to the VSV platform, we tested the use of IFN-β as a therapeutic transgene expressed from VSV as a novel treatment for mesothelioma. VSV-IFN-β showed significant therapy against AB12 murine mesotheliomas in the c...

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Optimization of Virotherapy for Cancer.

Bulletin of Mathematical Biology — Mon, 28 Sep 2009 23:00:00 +0100

Authors: Biesecker M, Kimn JH, Lu H, Dingli D, Bajzer Z Several viruses preferentially infect and replicate in cancer cells by usurping pathways that are defective in the tumor cell population. Such viruses have a potential as oncolytic agents. The aim of tumor virotherapy is that after injection of the replicating virus, it propagates in the tumor cell population with amplification. As a result, the oncolytic virus spreads to eradicate the tumor. The outcome of tumor virotherapy is determined by population dynamics and different from standard cancer therapy. Several models have been developed that provided considerable insights on the potential therapeutic scenarios. However, virotherapy is potentially risky since large amounts of a replicating virus are injected in the host with a ri...

An armed oncolytic adenovirus ZD55-IL-24 combined with ADM or DDP demonstrated enhanced antitumor effect in lung cancer.

Acta Oncologica — Thu, 03 Sep 2009 23:00:00 +0100

Conclusion. ZD55-IL-24 combined with ADM demonstrates improved killing effects against lung tumor xenograft. PMID: 19734998 [PubMed - as supplied by publisher] (Source: Acta Oncologica)

Overexpression of Newcastle disease virus (NDV) V protein enhances NDV production kinetics in chicken embryo fibroblasts.

Applied Microbiology and Biotechnology — Wed, 02 Sep 2009 23:00:00 +0100

Authors: Jang J, Hong SH, Choi D, Choi KS, Kang S, Kim IH Newcastle disease virus (NDV) is not only one of the most economically important pathogen of poultry but also has a potential as anticancer virotherapy. The role of NDV V protein in virus-production kinetics was investigated using DF-1 cell-based production system. The presence of an anti-interferon (IFN)-alpha antibody resulted in enhanced NDV production kinetics in a dose-dependent manner by blocking binding of NDV-induced IFN to its receptor. To prepare DF-1 cell whose cellular IFN signaling is blocked efficiently, stable cell lines expressing either lentogenic or velogenic NDV V protein known as an IFN antagonist were established. The overexpression of NDV V protein enhanced NDV production kinetics and expedited the rate of ...

Targeted Radiotherapy for Prostate Cancer with an Oncolytic Adenovirus Coding for Human Sodium Iodide Symporter.

Clinical Cancer Research — Mon, 24 Aug 2009 23:00:00 +0100

CONCLUSIONS: These results suggest that oncolytic adenovirus-mediated targeted radiotherapy might be a potentially useful option for enhancing the efficacy or adenoviral virotherapy. (Clin Cancer Res 2009;15(17):5396-403). PMID: 19706820 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

A chimeric adenovirus with an Ad 3 fiber knob modification augments glioma virotherapy

The Journal of Gene Medicine — Sun, 16 Aug 2009 23:00:00 +0100

Malignant gliomas remain refractory to treatment despite advances in chemotherapy and surgical techniques. Viral vectors developed to treat gliomas have had low transduction capabilities, limiting their use. Gliomas over-express CD46, CD80, and CD86, all of which bind adenovirus serotype 3.To increase the infectivity and replication of oncolytic vectors in malignant brain tumors, we created a conditionally replicating adenovirus, CRAd-Survivin-5/3, which contains a survivin promoter-driving E1A and a chimeric fiber consisting of adenovirus serotype 3 knob.In vitro, this modified CRAd showed ten- to 100-fold increased cytotoxicity against glioma cells. Ex vivo analysis of primary glioblastoma multiforme samples infected with CRAd-Survivin-5/3 showed an increase in cytotoxicity of 20-30% com...

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Virotherapy against malignant glioma stem cells

Cancer Letters — Thu, 30 Jul 2009 00:00:00 +0100

Abstract: Glioblastoma multiforme, the most common primary intracranial malignancy, is associated with very poor outcome despite advances in surgical techniques and chemo- and radiation therapy. Many novel treatment modalities are being investigated with varying amount of success. Evolution of cancer stem cell hypothesis provides a new venue for developmental therapeutics. In this review, we highlight the literature regarding the existence of glioma stem cells and their characteristics. We also discuss the potential for virotherapy, a novel therapeutic approach utilizing conditionally replicative viruses, to directly target this population of self-renewing cancer stem cells. (Source: Cancer Letters)

Construction of a MUC-1 promoter driven, conditionally replicating adenovirus that expresses the sodium iodide symporter (NIS) for gene therapy of breast cancer

Breast Cancer Research — Sun, 26 Jul 2009 23:00:00 +0100

Conclusions: This construct may allow multimodal therapy, combining virotherapy with radioiodine therapy to be developed as a novel treatment for breast and other MUC1 overexpressing cancers. (Source: Breast Cancer Research)

Enhanced cytotoxicity with a novel system combining the paclitaxel-2′-ethylcarbonate prodrug and an HSV amplicon with an attenuated replication-competent virus, HF10 as a helper virus

Cancer Letters — Wed, 15 Jul 2009 00:00:00 +0100

In this study, we investigated the efficacy of gene-directed enzyme prodrug therapy (GDEPT) using a novel system that combines the paclitaxel-2′-ethylcarbonate prodrug (TAX-2′-Et) and an HSV amplicon expressing rabbit-carboxylesterase (CES) with HF10 as a helper virus. This GDEPT system aims to produce high level of CES at the tumor site, resulting in efficient local conversion of the TAX-2′-Et prodrug into the active drug TAX [A. Nawa, T. Tanino, C. Lou, M. Iwaki, H. Kajiyama, K. Shibata, et al., Gene directed enzyme prodrug therapy for ovarian cancer: could GDEPT become a promising treatment against ovarian cancer?, Anti-Cancer Agents Med Chem 8 (2008) 232–239].We demonstrated that the green fluorescent protein (GFP) gene, as a trace maker, was more efficiently introduced by the ...

Transcriptionally regulated, prostate-targeted gene therapy for prostate cancer.

Advanced Drug Delivery Reviews — Sat, 27 Jun 2009 16:04:00 +0100

Authors: Lu Y Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in American males today. Novel and effective treatment such as gene therapy is greatly desired. The early viral based gene therapy uses tissue-nonspecific promoters, which causes unintended toxicity to other normal tissues. In this chapter, we will review the transcriptionally regulated gene therapy strategy for prostate cancer treatment. We will describe the development of transcriptionally regulated prostate cancer gene therapy in the following areas: (1) Comparison of different routes for best viral delivery to the prostate; (2) Study of transcriptionally regulated, prostate-targeted viral vectors: specificity and activity of the transgene under several different prost...

Cancer cell death by design: Apoptosis, autophagy and glioma virotherapy.

Autophagy — Sat, 27 Jun 2009 11:37:52 +0100

Authors: Tyler MA, Ulasov IV, Lesniak MS Autophagy has been defined as a mechanism by which oncolytic adenoviruses mediate cell killing in some cancers, including malignant glioma. Until recently, however, adenovirus replication was regarded as a process that induced classical apoptosis in the infected cell. We have assessed the method of conditionally replicating adenovirus (CRAd) death in a model of malignant glioma, considering both autophagy and apoptosis as possible mechanisms of virally-induced cell death. Our initial investigations indicated that autophagy was the predominant system in CRAd-induced cell death in glioma. This appeared to be the case in vitro; however, further investigation in vivo shows that CRAds are capable of inducing both apoptotic and autophagic cell death. ...

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Epithelial Phenotype Confers Resistance of Ovarian Cancer Cells to Oncolytic Adenoviruses

Cancer Research — Mon, 15 Jun 2009 04:00:00 +0100

We studied the susceptibility of primary ovarian cancer cells to oncolytic adenoviruses. Using gene expression profiling of cancer cells either resistant or susceptible to viral oncolysis, we discovered that the epithelial phenotype of ovarian cancer represents a barrier to infection by commonly used oncolytic adenoviruses targeted to coxsackie-adenovirus receptor or CD46. Specifically, we found that these adenovirus receptors were trapped in tight junctions and not accessible for virus binding. Accessibility to viral receptors was critically linked to depolarization and the loss of tight and adherens junctions, both hallmarks of epithelial-to-mesenchymal transition (EMT). We showed that specific, thus far little-explored adenovirus serotypes (Ad3, Ad7, Ad11, and Ad14) that use receptor(s)...

Engineered herpes simplex viruses efficiently infect and kill CD133+ human glioma xenograft cells that express CD111

Journal of Neuro-Oncology — Fri, 12 Jun 2009 11:30:23 +0100

We examined the ability of genetically engineered HSV to infect and kill cells that express CD133, a putative marker of glioma progenitor cells (GPC), to determine if GPC have an inherent therapeutic resistance to HSV. Expression of CD133 and CD111 (nectin-1), the major entry molecule for HSV, was variable in six human glioma xenografts, at initial disaggregation and after tissue culture. Importantly, both CD133+ and CD133− populations of glioma cells expressed CD111 in similar relative proportions in five xenografts, and CD133+ and CD133− glioma cell subpopulations were equally sensitive to killing in vitro by graded dilutions of wild-type HSV-1(F) or several different γ134.5-deleted viruses. GPC did not display an inherent resistance to HSV. While CD111 expression was an i...

An oncolytic adenovirus expressing herpes simplex virus-thymidine kinase for targeting cancer therapy: An in vitro evaluation

Chinese Journal of Cancer Research — Fri, 12 Jun 2009 10:57:19 +0100

Conclusion An oncolytic adenovirus plus the HSV-TK/GCV suicide gene system resulted in a significant improvement in treatment efficacy and it may offer important considerations in the development and preclinical assessments of oncolytic virotherapy. Content Type Journal ArticleCategory Cancer Gene TherapyDOI 10.1007/s11670-009-0090-zAuthors Fei-qun Zheng, Peking University School of Oncology, Beijing Cancer Hospital & Institute Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Interventional therapy Beijing 100142 ChinaYin Xu, Anhui Medical University Department of Biochemistry and Molecular Biology Hefei 230032 Anhui Province ChinaYi-de Qin, Anhui Medical University Department of Biochemistry and Molecular Biology Hefei...

[Microbiology] Inhibition of human tumor growth in mice by an oncolytic herpes simplex virus designed to target solely HER-2-positive cells

Proceedings of the National Academy of Sciences — Tue, 02 Jun 2009 04:00:00 +0100

Oncolytic virotherapy exploits the ability of viruses to infect, replicate into, and kill tumor cells. Among the viruses that entered... (Source: Proceedings of the National Academy of Sciences)

Targeted genetic and viral therapy for advanced head and neck cancers.

Drug Discovery Today — Sun, 31 May 2009 23:00:00 +0100

Authors: Huang PI, Chang JF, Kirn DH, Liu TC Head and neck cancers usually present with advanced disease and novel therapies are urgently needed. Genetic therapy aims at restoring malfunctioned tumor suppressor gene(s) or introducing proapoptotic genes. Oncolytic virotherapeutics induce multiple cycles of cancer-specific virus replication, followed by oncolysis, virus spreading and infection of adjacent cancer cells. Oncolytic viruses can also be armed to express therapeutic transgene(s). Recent advances in preclinical and clinical studies are revealing the potential of both therapeutic classes for advanced head and neck cancers, including the approval of two products (Gendicine and H101) by a governmental agency. This review summarizes the available clinical data to date and discusses...

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Pharmacologic and Chemical Adjuvants in Tumor Virotherapy

Chemical Reviews — Sat, 23 May 2009 04:03:21 +0100

Chemical Reviews, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Chemical Reviews)

Adenoviral virotherapy for malignant brain tumors

Expert Opinion: Expert Opinion on Biological Therapy: Table of Contents — Wed, 20 May 2009 12:20:17 +0100

Expert Opinion on Biological Therapy , June 2009, Vol. 9, No. 6, Pages 737-747. (Source: Expert Opinion: Expert Opinion on Biological Therapy: Table of Contents)

Drug-regulatable cancer cell death induced by BID under control of the tissue-specific, lung cancer-targeted TTS promoter system

International Journal of Cancer — Sun, 17 May 2009 23:00:00 +0100

Gene therapy and virotherapy are among the approaches currently being used to treat lung cancer. The success of cancer gene therapy depends on treatments where different types of tumors can be selectively targeted and destroyed without affecting normal cells and tissue. Previously, we described a promoter system (TTS) that we designed that is specifically targeted to lung cancer cells but which does not affect other types of cells including stem cells. In our study, we have enhanced the utility of the TTS system by inserting the pro-apoptotic gene BH3 domain interacting death agonist (Bid) into the TTS promoter system (TTS/Bid) to create a drug regulatable lung cancer-specific gene therapy. A recombinant adenoviral vector was used to introduce TTS/Bid (Ad-TTS/Bid) into lung cancer cells. B...

Advancements in adenoviral based virotherapy for ovarian cancer.

Advanced Drug Delivery Reviews — Mon, 04 May 2009 23:00:00 +0100

Authors: Matthews KS, Alvarez RD, Curiel DT Ovarian cancer is a leading gynecologic malignancy with relatively grim survival statistics. There is a significant need for the development of new treatment options for this malignancy. The development of virotherapy as a treatment option for ovarian cancer has the potential to improve patient survival. Adenoviruses have multiple advantages as vectors for virotherapy including a well-understood structure and the ability to infect cells easily. We will outline the advances in virotherapy in the treatment of ovarian cancer, with particular attention directed toward adenoviral vectors. PMID: 19422865 [PubMed - as supplied by publisher] (Source: Advanced Drug Delivery Reviews)

Human precision-cut liver tumor slices as a tumor patient-individual predictive test system for oncolytic measles vaccine viruses.

International Journal of Oncology — Thu, 30 Apr 2009 23:00:00 +0100

In conclusion, the PCLS technology is suitable to perform a tumor-patient individualized preselection of oncolytic agents prior to clinical virotherapeutic applications. PMID: 19360338 [PubMed - in process] (Source: International Journal of Oncology)

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Tumor-associated macrophages infiltrate plasmacytomas and can serve as cell carriers for oncolytic measles virotherapy of disseminated myeloma

American Journal of Hematology — Tue, 28 Apr 2009 23:00:00 +0100

In multiple myeloma, some of the neoplastic plasma cells are diffusely dispersed among the normal bone marrow cells (bone marrow resident), whereas others are located in discrete, well-vascularized solid tumors (plasmacytomas) that may originate in bone or soft tissue. Interactions between bone marrow-resident myeloma cells and bone marrow stromal cells (BMSCs) are important determinants of myeloma pathogenesis. However, little is known of the factors sustaining myeloma growth and cell viability at the centers of expanding plasmacytomas, where there are no BMSCs. Histologic sections of 22 plasmacytomas from myeloma patients were examined after immunostaining. Abundant CD68+, CD163+, S100-negative macrophage infiltrates were identified in all tumors, accompanied by scattered collections of ...

Measles virotherapy in prostate cancer treatment: a novel antitumor approach

Future Virology — Mon, 27 Apr 2009 10:54:03 +0100

Future Virology , May 2009, Vol. 4, No. 3, Pages 203-207. (Source: Future Virology)

The emergence of combinatorial strategies in the development of RNA oncolytic virus therapies

Cellular Microbiology — Mon, 20 Apr 2009 04:00:00 +0100

Oncolytic viruses (OVs) represent an exciting new biological approach to cancer therapy. In particular, RNA viruses have emerged as potent agents for oncolytic virotherapy because of their capacity to specifically target and destroy tumour cells while sparing normal cells and tissues. Several barriers remain in the development of OV therapy, including poor penetration into the tumour mass, inefficient virus replication in primary cancers, and tumour-specific resistance to OV-mediated killing. The combination of OVs with cytotoxic agents, such as small molecule inhibitors of signalling or immunomodulators, as well as stealth delivery of therapeutic viruses have shown promise as novel experimental strategies to overcome resistance to viral oncolysis. These agents complement OV therapy by unb...

Prostate-specific membrane antigen retargeted measles virotherapy for the treatment of prostate cancer

The Prostate — Sat, 18 Apr 2009 04:00:00 +0100

Live attenuated vaccine strain of measles virus (MV) has promising antitumor activity and is undergoing clinical testing in three different phase I cancer trials. The virus uses one of two receptors, CD46 which is ubiquitously expressed on all nucleated cells or CD150 which is expressed on immune cells, to infect cells. To minimize potential toxicity due to indiscriminate infection of normal cells, we have generated a fully retargeted MV that infects cells exclusively through the prostate-specific membrane antigen (PSMA) receptor, which is overexpressed on prostate cancer cells and tumor neovasculature.A single-chain antibody (scFv) specific for the extracellular domain of PSMA (J591) was inserted as a C-terminal extension on the MV attachment protein. Specificity of infection by the PSMA ...

VSV virotherapy improves chemotherapy by triggering apoptosis due to proteasomal degradation of Mcl-1

Gene Therapy — Thu, 16 Apr 2009 04:00:00 +0100

Authors: P Schache, E Gürlevik, N Strüver, N Woller, N Malek, L Zender, M Manns, T Wirth, F Kühnel & S Kubicka (Source: Gene Therapy)

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Adenovirus-based virotherapy enabled by cellular YB-1 expression in vitro and in vivo

Cancer Gene Therapy — Fri, 10 Apr 2009 04:00:00 +0100

Authors: E Rognoni, M Widmaier, C Haczek, K Mantwill, R Holzmüller, B Gansbacher, A Kolk, T Schuster, R M Schmid, D Saur, A Kaszubiak, H Lage & P S Holm (Source: Cancer Gene Therapy)

CRAdRGDflt-IL24 virotherapy in combination with chemotherapy of experimental glioma

Cancer Gene Therapy — Fri, 10 Apr 2009 04:00:00 +0100

Authors: L N Kaliberova, V Krendelchtchikova, D K Harmon, C R Stockard, A S Petersen, J M Markert, G Y Gillespie, W E Grizzle, D J Buchsbaum & S A Kaliberov (Source: Cancer Gene Therapy)

Telomerase-specific virotheranostics for human head and neck cancer.

Clinical Cancer Research — Wed, 01 Apr 2009 04:00:00 +0100

CONCLUSIONS: These results illustrate the potential of telomerase-specific oncolytic viruses for a novel therapeutic and diagnostic approach, termed theranostics, for human SCCHN. PMID: 19318473 [PubMed - in process] (Source: Clinical Cancer Research)

Cross-infection of tumor cells by contact with T lymphocytes loaded with Newcastle disease virus.

International Journal of Oncology — Fri, 20 Mar 2009 09:16:34 +0100

We describe for the first time in an in vitro co-culture system that T lymphocytes can be loaded with Newcastle disease virus (NDV) in such a way that the virus load will be transferred to the tumor target cells upon contact of the T cells with tumor cells. The effectiveness of this NDV 'hitchhiking' on T cells can be influenced by the amount of virus, the ratio of T cells to tumor cells, the activation status of the T cells and by the virulence of the virus as shown by flow cytometry, quantitative real-time PCR and fluorescence microscopy. In a tumor neutralization assay in vitro, monolayers of human tumor cells could be completely and effectively destroyed by the addition of polyclonally activated human T cells loaded with oncolytic NDV. This process involves the formation of large T cel...

A novel recombinant vaccinia virus expressing the human norepinephrine transporter retains oncolytic potential and facilitates deep tissue imaging.

Molecular Medicine — Sat, 14 Mar 2009 04:00:00 +0100

Authors: Chen N, Zhang Q, Yu YA, Stritzker J, Brader P, Schirbel A, Samnick S, Serganova I, Blasberg R, Fong Y, Szalay AA Noninvasive and repetitive monitoring of a virus in target tissues and/or specific organs of the body is highly desirable for the development of safe and efficient cancer virotherapeutics. We have previously shown that the oncolytic vaccinia virus GLV-1h68 can target and eradicate human tumors in mice and that its therapeutic effects can be monitored using optical imaging. Here, we report on the development of a novel recombinant vaccinia virus (VACV) GLV-1h99, a derivative of GLV-1h68, which was constructed to carry the human norepinephrine transporter gene (hNET) under the VACV synthetic early promoter placed at the F14.5L locus for deep tissue imaging. The hNET p...

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Combination of adenoviral virotherapy and temozolomide chemotherapy eradicates malignant glioma through autophagic and apoptotic cell death in vivo

British Journal of Cancer AOP — Tue, 10 Mar 2009 04:00:00 +0100

Authors: I V Ulasov, A M Sonabend, S Nandi, A Khramtsov, Y Han & M S Lesniak (Source: British Journal of Cancer AOP)

Enhancement of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying MDA-7/IL-24.

Acta Pharmacologica Sinica — Mon, 09 Mar 2009 04:00:00 +0100

Conclusion:This study showed that ZD55-IL-24 conjugated with cisplatin exhibited a remarkably increased cytotoxic and apoptosis-inducing effect in cancer cells and significantly reduced the toxicity in normal cells through the use of a reduced dose.Acta Pharmacologica Sinica advance online publication, 9th March 2009; doi: 10.1038/aps.2009.16. PMID: 19270721 [PubMed - as supplied by publisher] (Source: Acta Pharmacologica Sinica)

Potent antitumor activity of double-regulated oncolytic adenovirus-mediated ST13 for colorectal cancer

Cancer Science — Sun, 01 Mar 2009 05:00:00 +0100

Following targeted gene virotherapy, the suppression of tumorigenicity 13 (ST13) gene was inserted into the double-regulated oncolytic adenovirus SG500 to ensure more safety and potent antitumor activity against colorectal cancer in vitro and in vivo. We generated the ST13-expressing oncolytic adenovirus SG500-ST13, with which colorectal carcinoma cell lines SW620 and HCT116, and the lung fibroblast cell line WI38, were infected. Crystal violet staining was carried out to detect the cytopathic effect in cells, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method was used to assay cell viability. The effect of apoptosis induced by SG500-ST13 was confirmed by Hoechst staining and the TdT-mediated dUTP-biotin nick-end labeling method. To further identify the antitumor e...

Measles Virus May Be Effective Prostate Cancer Treatment

Cancercompass News: Prostate Cancer — Fri, 20 Feb 2009 11:02:02 +0100

A new study appearing in The Prostate has found that certain measles virus vaccine strain derivatives, including a strain known as MV-CEA, may prove to be an effective treatment for patients with advanced prostate cancer. The findings show that this type of treatment, called virotherapy, can effectively infect, replicate in and kill prostate cancer cells. Prostate cancer is a leading cause death among males in the western world. It is currently the second most common cause of cancer-related deaths among American men with 186,320 new cases and 28,660 deaths expected to be recorded in 2008. A sizeable proportion of these patients ultimately relapse, with a 5-year failure rate for treatment ranging from 14 to 34 percent. No curative therapy... (Source: Cancercompass News: Prostate Cancer)

Combination of oncolytic adenoviral therapy with chemotherapy for enhanced breast cancer cell killing.

Cancer Research — Thu, 19 Feb 2009 05:00:00 +0100

In this study, we investigated a combination treatment of breast cancer cells with Ad5-4-RGD and Docetaxel, a microtubule-stabilizing taxane that is being used in the clinic for the treatment of breast and prostate cancers and small cell carcinoma of the lung. Our results indicate a synergistic effect between Docetaxel and Ad5-24-RGD in breast cancer cell killing at a lower dose than either agent alone. These results suggest that viral replication was not inhibited by this chemotherapy treatment and that chemotherapy could reduce the amount of viral particles needed to help eradicate the tumor. Administration of lower viral loads would simultaneously improve safety and decrease immunogenicity of the vector. Likewise lower doses of chemotherapy agents would decrease toxicity and side effect...

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Telomerase-specific virotherapy for human squamous cell carcinoma

Expert Opinion: Expert Opinion on Biological Therapy: Table of Contents — Fri, 13 Feb 2009 13:48:05 +0100

Expert Opinion on Biological Therapy , March 2009, Vol. 9, No. 3, Pages 321-329. (Source: Expert Opinion: Expert Opinion on Biological Therapy: Table of Contents)

Antitumoral Immune Response by Recruitment and Expansion of Dendritic Cells in Tumors Infected with Telomerase-Dependent Oncolytic Viruses

Cancer Research — Thu, 12 Feb 2009 05:00:00 +0100

Virotherapy can potentially be used to induce tumor-specific immune responses and to overcome tumor-mediated tolerance mechanisms because apoptotic tumor cells are exposed together with viral danger signals during oncolysis. However, insufficient numbers of dendritic cells (DC) present at the site of oncolysis can limit a tumor-specific immune response and the resulting therapeutic benefit. We investigated MHC class I peptide–specific immune responses against model antigens ovalbumin (OVA) and hemagglutinin (HA) in mouse tumor models that support efficient replication of the oncolytic adenovirus hTert-Ad. Virotherapy resulted in peptide-specific cytotoxic T-cell responses against intracellular tumor antigens. Triggering of DC and T-cell infiltration to the oncolytic tumors by macroph...

Armed replicating adenoviruses for cancer virotherapy

Cancer Gene Therapy — Sun, 08 Feb 2009 08:48:26 +0100

Authors: J J Cody & J T Douglas (Source: Cancer Gene Therapy)

Antitumoral Immune Response by Recruitment and Expansion of Dendritic Cells in Tumors Infected with Telomerase-Dependent Oncolytic Viruses.

Cell Research — Tue, 03 Feb 2009 05:00:00 +0100

Authors: Ramakrishna E, Woller N, Mundt B, Knocke S, Gürlevik E, Saborowski M, Malek N, Manns MP, Wirth T, Kühnel F, Kubicka S Virotherapy can potentially be used to induce tumor-specific immune responses and to overcome tumor-mediated tolerance mechanisms because apoptotic tumor cells are exposed together with viral danger signals during oncolysis. However, insufficient numbers of dendritic cells (DC) present at the site of oncolysis can limit a tumor-specific immune response and the resulting therapeutic benefit. We investigated MHC class I peptide-specific immune responses against model antigens ovalbumin (OVA) and hemagglutinin (HA) in mouse tumor models that support efficient replication of the oncolytic adenovirus hTert-Ad. Virotherapy resulted in peptide-specific cytot...

A multiscale mathematical model for oncolytic virotherapy.

Cell Research — Sat, 31 Jan 2009 05:32:15 +0100

Authors: Paiva LR, Binny C, Ferreira SC, Martins ML One of the most promising strategies to treat cancer is attacking it with viruses. Oncolytic viruses can kill tumor cells specifically or induce anticancer immune response. A multiscale model for virotherapy of cancer is investigated through simulations. It was found that, for intratumoral virus administration, a solid tumor can be completely eradicated or keep growing after a transient remission. Furthermore, the model reveals undamped oscillatory dynamics of tumor cells and virus populations, which demands new in vivo and in vitro quantitative experiments aiming to detect this oscillatory response. The conditions for which each one of the different tumor responses dominates, as well as the occurrence probabilities for the other nond...

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A Multiscale Mathematical Model for Oncolytic Virotherapy

Cancer Research — Thu, 29 Jan 2009 05:00:00 +0100

One of the most promising strategies to treat cancer is attacking it with viruses. Oncolytic viruses can kill tumor cells specifically or induce anticancer immune response. A multiscale model for virotherapy of cancer is investigated through simulations. It was found that, for intratumoral virus administration, a solid tumor can be completely eradicated or keep growing after a transient remission. Furthermore, the model reveals undamped oscillatory dynamics of tumor cells and virus populations, which demands new in vivo and in vitro quantitative experiments aiming to detect this oscillatory response. The conditions for which each one of the different tumor responses dominates, as well as the occurrence probabilities for the other nondominant therapeutic outcomes, were determined. From a cl...

Prostate Cancer: Measles Virus May Be Effective Treatment

Health News from Medical News Today — Thu, 22 Jan 2009 13:00:00 +0100

Measles Virus May Be Effective Prostate Cancer Treatment

Huliq Health News — Thu, 22 Jan 2009 11:26:00 +0100

Coagulation Factors Determine Tumor Transduction In Vivo

Human Gene Therapy — Sat, 29 Nov 2008 12:21:22 +0100

Human Gene Therapy , Vol. 0, No. 0: 1-6. A critical obstacle for efficient gene therapy and virotherapy of cancer with adenoviral vectors and oncolytic adenoviruses is to target tumor cells in vivo. Recent reports indicate that, contrary to the natural airborne infection of epithelial cells with ... (Source: Human Gene Therapy)

Inhibition of renal cancer cell growth by oncolytic adenovirus armed short hairpin RNA targeting hTERT gene.

Cancer Biology and Therapy — Thu, 27 Nov 2008 15:28:37 +0100

In this study, we constructed a novel oncolytic adenovirus-based shRNA expression system, ZD55-hTERT, and to explore ZD55-hTERT-mediated RNAi for hTERT gene silencing. Our results showed that ZD55-hTERT could induce silencing of hTERT gene effectively, allow for efficient tumor-specific viral replication and induce the apoptosis of tumor cells effectively in vitro and in nude mice. We conclude that combining shRNA gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and shRNA antitumor responses. PMID: 19029834 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy)

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Oncolytic virotherapy for advanced liver tumours

Journal of Cellular and Molecular Medicine — Wed, 22 Oct 2008 23:00:00 +0100

Introduction Pre-clinical studies Clinical studies Challenges for the use of virotherapy agents in liver tumour treatment Future directions Primary and metastatic neoplasms of the liver account for more than a million deaths per year worldwide. Despite decades of research, effective novel therapies for these cancers are urgently needed. Oncolytic virotherapeutics represent a novel class of pharmacophore that holds promise for the treatment of hepatic neoplasms. Cancer-specific replication is followed by oncolysis, virus spreading and infection of adjacent cancer cells. This process is then repeated. Virotherapeutics target multiple genetic pathways involved in carcino-genesis, and demonstrate activity against apoptosis-resistant tumour cells. This platform can also exploit the advantage of...

Oncolytic Semliki Forest Virus Vector as a Novel Candidate against Unresectable Osteosarcoma

Cancer Research — Wed, 15 Oct 2008 04:00:00 +0100

Oncolytic viruses are a promising tool for treatment of cancer. We studied an oncolytic Semliki Forest virus (SFV) vector, VA7, carrying the enhanced green fluorescent protein gene (EGFP), as a novel virotherapy candidate against unresectable osteosarcoma. The efficiency and characteristics of the VA7-EGFP treatment were compared with a widely studied oncolytic adenovirus, Ad524, both in vitro and in vivo. VA7-EGFP resulted in more rapid oncolysis and was more efficient at low multiplicities of infection (MOI) when compared with Ad524 in vitro. Yet, in MG-63 cells, a subpopulation resistant to the VA7-EGFP vector emerged. In subcutaneous human osteosarcoma xenografts in nude mice treatment with either vector reduced tumor size, whereas tumors in control mice expanded quickly. The VA7-EGFP&...

Bevacizumab Increases Viral Distribution in Human Anaplastic Thyroid Carcinoma Xenografts and Enhances the Effects of E1A-Defective Adenovirus dl922-947.

Clinical Cancer Research — Wed, 15 Oct 2008 04:00:00 +0100

CONCLUSIONS: Our data showed that dl922-947 had a higher oncolytic activity compared with dl1520 in anaplastic thyroid carcinoma cell lines and might represent a better option for virotherapy of anaplastic thyroid carcinoma. Moreover, bevacizumab increased the oncolytic effects of dl922-947 by enhancing viral distribution in tumors. The results described herein encourage the use of the dl922-947 virus in combination with bevacizumab. PMID: 18927290 [PubMed - in process] (Source: Clinical Cancer Research)

With Help Of New Compound Viral 'Magic Bullet' Targets Cancer Cells

Infectious Diseases / Bacteria / Viruses News From Medical News Today — Thu, 18 Sep 2008 08:00:00 +0100

Researchers at McGill University and the affiliated Lady Davis Research Institute of the Jewish General Hospital - along with colleagues at the University of Ottawa and the Ottawa Health Research Institute (OHRI) - report a significant breakthrough in the use of viruses to target and destroy cancer cells, a field known as oncolytic virotherapy. Their results were published in the September early edition of the Proceedings of the National Academy of Sciences (PNAS). (Source: Infectious Diseases / Bacteria / Viruses News From Medical News Today)