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In vivo major histocompatibility complex class I (MHCI) expression on MHCIlow tumor cells is regulated by gammadelta T and NK cells during the early steps of tumor growth.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cell surface expression of MHC class I molecules by tumor cells is determinant in the interplay between tumor cells and the immune system. Nevertheless, the mechanisms which regulate MHCI expression on tumor cells are not clear. We previously showed that immune innate cells from the spleen can regulate MHCI expression on MHCI(low) tumor cells. Here, using the murine model of B16 melanoma, we demonstrate that the MHCI status of tumor cells in vivo is regulated by the microenvironment. In subcutaneous grafts, induction of MHCI molecules on tumor cells is concomitant to the recruitment of lymphocytes and relies on an IFNg...
Source: Cancer Immunity - November 6, 2009 Category: Cancer & Oncology Authors: Riond J, Rodriguez S, Nicolau ML, al Saati T, Gairin JE Tags: Cancer Immun Source Type: journals

In vivo major histocompatibility complex class I (MHCI) expression on MHCI(low) tumor cells is regulated by gammadelta T and NK cells during the early steps of tumor growth.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cell surface expression of MHC class I molecules by tumor cells is determinant in the interplay between tumor cells and the immune system. Nevertheless, the mechanisms which regulate MHCI expression on tumor cells are not clear. We previously showed that immune innate cells from the spleen can regulate MHCI expression on MHCI(low) tumor cells. Here, using the murine model of B16 melanoma, we demonstrate that the MHCI status of tumor cells in vivo is regulated by the microenvironment. In subcutaneous grafts, induction of MHCI molecules on tumor cells is concomitant to the recruitment of lymphocytes and relies on an IFNg...
Source: Cancer Immunity - November 4, 2009 Category: Cancer & Oncology Authors: Riond J, Rodriguez S, Nicolau ML, Al Saati T, Gairin JE Tags: Cancer Immun Source Type: journals

Real-time PCR analysis of genes encoding tumor antigens in esophageal tumors and a cancer vaccine.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tumor antigens are the primary target of therapeutic cancer vaccines. We set out to define and compare the expression pattern of tumor antigen genes in esophagus carcinoma biopsies and in an allogeneic tumor lysate-based cancer vaccine, MelCancerVac. Cells used for vaccine production were treated with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) to determine whether this treatment could improve the profile of tumor antigen genes expressed in these cells. In addition, the presence of MAGE-A tumor antigen protein was evaluated in the purified tumor cell lysate used in the production of the vacci...
Source: Cancer Immunity - October 11, 2009 Category: Cancer & Oncology Authors: Weinert BT, Krishnadath KK, Milano F, Pedersen AW, Claesson MH, Zocca MB Tags: Cancer Immun Source Type: journals

Correlation of high and decreased NY-ESO-1 immunity to spontaneous regression and subsequent recurrence in a lung cancer patient.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We show correlation between strong and decreased NY-ESO-1-specific immunity with spontaneous regression and subsequent recurrence, respectively, in a long-surviving patient with an NY-ESO-1-expressing lung adenocarcinoma. An integrated immune response consisting of IgG antibody, as well as CD4 and CD8 T cells, against NY-ESO-1 was observed at the time of spontaneous regression of multiple pleural metastases. After tumor dormancy for 3 years, the tumor started to progress. IgG antibody levels and the number of CD4 and CD8 T cells against NY-ESO-1 decreased, but were still detectable. On the other hand, the number of Fox...
Source: Cancer Immunity - October 3, 2009 Category: Cancer & Oncology Authors: Isobe M, Eikawa S, Uenaka A, Nakamura Y, Kanda T, Kohno S, Kuzushima K, Nakayama E Tags: Cancer Immun Source Type: journals

Soluble MHC-peptide complexes: tools for the monitoring of T cell responses in clinical trials and basic research.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Soluble MHC-peptide complexes, commonly known as tetramers, allow the detection and isolation of antigen-specific T cells. Although other types of soluble MHC-peptide complexes have been introduced, the most commonly used MHC class I staining reagents are those originally described by Altman and Davis. As these reagents have become an essential tool for T cell analysis, it is important to have a large repertoire of such reagents to cover a broad range of applications in cancer research and clinical trials. Our tetramer collection currently comprises 228 human and 60 mouse tetramers and new reagents are continuously bei...
Source: Cancer Immunity - September 28, 2009 Category: Cancer & Oncology Authors: Guillaume P, Dojcinovic D, Luescher IF Tags: Cancer Immun Source Type: journals

Expression and serum immunoreactivity of developmentally restricted differentiation antigens in epithelial ovarian cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cancer-embryo antigens or developmentally restricted differentiation antigens (DRDAGs), such as PLAC1 (CT92) and developmental pluripotency associated-2 (DPPA2/CT100), are expressed in pluripotent embryonic cells. They are also recognized as cancer-testis antigens (CT) which are proteins normally expressed only in the human germ line but that are also present in a significant subset of malignant tumors. These antigens may prove to be markers of 'repopulating' cells with stem cell-like characteristics and could be critical targets for immunotherapy in epithelial ovarian cancer (EOC). Our objective was to define the freq...
Source: Cancer Immunity - August 27, 2009 Category: Cancer & Oncology Authors: Tchabo NE, Mhawech-Fauceglia P, Caballero OL, Villella J, Beck AF, Miliotto AJ, Liao J, Andrews C, Lele S, Old LJ, Odunsi K Tags: Cancer Immun Source Type: journals

CD44+ cancer cells express higher levels of the anti-apoptotic protein Bcl-2 in breast tumours.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Breast tumours consist of phenotypically diverse populations of breast cancer cells of which only a minority has the ability to form new tumours. The capacity for breast tumour development has been shown to be restricted to breast cancer stem cells with the CD44+/CD24(-/low) phenotype. These cells can resist apoptosis through mechanisms such as the regulation of Bcl-2. Identification of this population of cells is important because of its implication in the development of new therapeutic strategies. One hundred and forty-six primary operable breast cancer patients were investigated in order to identify the population o...
Source: Cancer Immunity - June 27, 2009 Category: Cancer & Oncology Authors: Madjd Z, Mehrjerdi AZ, Sharifi AM, Molanaei S, Shahzadi SZ, Asadi-Lari M Tags: Cancer Immun Source Type: journals

Safety and immunogenicity of a human and mouse gp100 DNA vaccine in a phase I trial of patients with melanoma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A differentiation antigen commonly expressed on melanoma cells, gp100 is the target of infiltrating T cells. We conducted a phase I randomized cross-over trial of melanoma patients with either xenogeneic (mouse) or human gp100 plasmid DNA injected intramuscularly at three dosages (100, 500 or 1,500 microg) every three weeks for three doses. After the first three injections, patients were then immunized three times with gp100 from the other species. Peripheral blood samples were analyzed at various time points following 10-day culture with gp100 peptides using multi-parametric flow cytometry. A total of 19 patients were...
Source: Cancer Immunity - June 27, 2009 Category: Cancer & Oncology Authors: Yuan J, Ku GY, Gallardo HF, Orlandi F, Manukian G, Rasalan TS, Xu Y, Li H, Vyas S, Mu Z, Chapman PB, Krown SE, Panageas K, Terzulli SL, Old LJ, Houghton AN, Wolchok JD Tags: Cancer Immun Source Type: journals

Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human melanoma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tumors contain variable numbers of lymphocytes, referred to as tumor infiltrating lymphocytes (TILs). In melanoma, the intensity of this lymphocytic infiltrate is believed to correlate with outcome, though there is some debate about the applicability of this finding for all melanomas. Much research has gone into classifying TILs with respect to antigen receptor structure and the antigen to which melanoma-specific T cells react. However, these studies for the most part did not immunophenotype TILs, and recent data has revealed that the composition of tumoral lymphocytes is not homogenous, but rather represents varying c...
Source: Cancer Immunity - April 7, 2009 Category: Cancer & Oncology Authors: Oble DA, Loewe R, Yu P, Mihm MC Tags: Cancer Immun Source Type: journals

Sequential cancer immunotherapy: targeted activity of dimeric TNF and IL-8.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Polymorphonuclear neutrophils (PMNs) are potent effectors of inflammation and their attempts to respond to cancer are suggested by their systemic, regional and intratumoral activation. We previously reported on the recruitment of CD11b+ leukocytes due to tumor site-specific enrichment of TNF activity after intravenous administration of a dimeric TNF immunokine with specificity for fibroblast activation protein (FAP). However, TNF-induced chemo-attraction and extravasation of PMNs from blood into the tumor is a multistep process essentially mediated by interleukin 8. With the aim to amplify the TNF-induced and IL-8-medi...
Source: Cancer Immunity - March 11, 2009 Category: Cancer & Oncology Authors: Bauer S, Adrian N, Siebenborn U, Fadle N, Plesko M, Fischer E, Wüest T, Stenner F, Mertens JC, Knuth A, Ritter G, Old LJ, Renner C Tags: Cancer Immun Source Type: journals

The localization and density of immune cells in primary tumors of human metastatic colorectal cancer shows an association with response to chemotherapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In situ immunohistochemical staining of tumor-infiltrating immune cells in large cohorts of human colorectal cancers has recently supported the hypothesis that the adaptive immune response influences the behavior of human tumors. Tumor-infiltrating immune cells therefore represent a valuable prognostic marker for patients with colorectal cancer, with a high density of immune cells being associated with a good outcome independently of other established prognostic markers. The aim of the present study was to investigate the correlation between infiltrates of immune cells, in either the primary tumor or (where available) ...
Source: Cancer Immunity - February 20, 2009 Category: Cancer & Oncology Authors: Halama N, Michel S, Kloor M, Zoernig I, Pommerencke T, von Knebel Doeberitz M, Schirmacher P, Weitz J, Grabe N, Jäger D Tags: Cancer Immun Source Type: journals

Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in head and neck cancers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The expanding and established literature that correlates tumor infiltrating lymphocytes (TILs) with outcomes of patients with solid tumors has contributed greatly to the appreciation of the interaction between the host immune system with neoplastic growth. This analysis has been limited to specific tumors, such as melanoma and ovarian cancer, and our understanding of TILs in relation to many other malignancies has yet to be explored. We review one less well studied malignancy, head and neck squamous cell carcinoma (HNSCC), and the initial attempts to examine the impact of TILs on outcomes of these patients. To provide ...
Source: Cancer Immunity - December 7, 2008 Category: Cancer & Oncology Authors: Uppaluri R, Dunn GP, Lewis JS Tags: Cancer Immun Source Type: journals

Identification of the HERV-K gag antigen in prostate cancer by SEREX using autologous patient serum and its immunogenicity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The prostate cancer HERV-K gag-related NGO-Pr-54 antigen was identified by SEREX analysis using autologous patient serum. NGO-Pr-54 mRNA was observed to be faintly expressed in normal prostate and strongly expressed in a variety of cancers, including ovarian cancer (5/8), prostate cancer (6/9), and leukemia (5/14). A phage plaque assay showed that a strong reaction was constantly observed with clone ZH042 in which the 5' end of NGO-Pr-54 is deleted, suggesting that it contained the sequence coding for the protein product. A TI-35 mAb was produced using a recombinant protein (438 aa) deduced from the sequence of ZH042. ...
Source: Cancer Immunity - November 15, 2008 Category: Cancer & Oncology Authors: Ishida T, Obata Y, Ohara N, Matsushita H, Sato S, Uenaka A, Saika T, Miyamura T, Chayama K, Nakamura Y, Wada H, Yamashita T, Morishima T, Old LJ, Nakayama E Tags: Cancer Immun Source Type: journals

The innate immune system recognizes and regulates major histocompatibility complex class I (MHCI) expression on MHCIlow tumor cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tumor cells and the immune system play a lethal "pas de deux" during tumor development. However, it is not clear which role the innate immune system plays in these interactions. We studied the interaction of normal spleen cells (NSCs) with tumor cells expressing low levels of MHCI on the cell surface. This interaction induces increased MHCI expression on the MHCI(low) tumor cells by a cell-cell contact-dependent, IFN-gamma-mediated mechanism. The effector cells responsible for the increased IFN-gamma production were identified as CD4+ CD1d-independent NKT cells, NK1.1+ NK cells and CD4+ CD11c+ DCs. The possible three c...
Source: Cancer Immunity - September 16, 2008 Category: Cancer & Oncology Authors: Rubin B, Riond J, Courtiade L, Roullet N, Gairin JE Tags: Cancer Immun Source Type: journals

The innate immune system recognizes and regulates major histocompatibility complex class I (MHCI) expression on MHCI(low) tumor cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tumor cells and the immune system play a lethal "pas de deux" during tumor development. However, it is not clear which role the innate immune system plays in these interactions. We studied the interaction of normal spleen cells (NSCs) with tumor cells expressing low levels of MHCI on the cell surface. This interaction induces increased MHCI expression on the MHCI(low) tumor cells by a cell-cell contact-dependent, IFN-gamma-mediated mechanism. The effector cells responsible for the increased IFN-gamma production were identified as CD4+ CD1d-independent NKT cells, NK1.1+ NK cells and CD4+ CD11c+ DCs. The possible three c...
Source: Cancer Immunity - September 13, 2008 Category: Cancer & Oncology Authors: Rubin B, Riond J, Courtiade L, Roullet N, Gairin JE Tags: Cancer Immun Source Type: journals

Prolonged survival of patients with lung adenocarcinoma expressing XAGE-1b and HLA class I antigens.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
XAGE-1b is a cancer/testis antigen that has been shown to be expressed at a significant frequency and to be immunogenic in non-small cell lung cancer (NSCLC). In the present study, we investigated correlations between XAGE-1b expression and NSCLC patient survival. XAGE-1b expression was examined immunohistochemically using USO9-13, an anti-XAGE-1b monoclonal antibody, in 121 NSCLCs (83 adenocarcinomas and 38 other histological types). XAGE-1b expression was observed in 27 (32.5%) adenocarcinoma specimens. In the other histological types, positive staining was observed in only 1 specimen. HLA class I expression in these...
Source: Cancer Immunity - August 31, 2008 Category: Cancer & Oncology Authors: Kikuchi E, Yamazaki K, Nakayama E, Sato S, Uenaka A, Yamada N, Oizumi S, Dosaka-Akita H, Nishimura M Tags: Cancer Immun Source Type: journals

Activation of NK cells by extracellular heat shock protein 70 through induction of NKG2D ligands on dendritic cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, HSP70 of both autologous and allogeneic origin was found to stimulate IFN-gamma production from peripheral blood mononuclear cells of CML patients, as well as of normal subjects. Further investigations demonstrated that the activity of HSP70 was dependent on both NK cells and dendritic cells (DCs). HSP70 did not induce significant IFN-gamma production from either NK cells or DCs alone. Mechanistically, we found that HSP70-mediated DC-NK cell crosstalk required cell-cell contact, which could be inhibited completely by neutralizing antibody against NK activating receptor NKG2D. The significance of NKG2D was fu...
Source: Cancer Immunity - July 13, 2008 Category: Cancer & Oncology Authors: Qiao Y, Liu B, Li Z Tags: Cancer Immun Source Type: journals

Identification of tumor-associated antigens by large-scale analysis of genes expressed in human colorectal cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Despite the high prevalence of colon cancer in the world and the great interest in targeted anti-cancer therapy, only few tumor-specific gene products have been identified that could serve as targets for the immunological treatment of colorectal cancers. The aim of our study was therefore to identify frequently expressed colon cancer-specific antigens. We performed a large-scale analysis of genes expressed in normal colon and colon cancer tissues isolated from colorectal cancer patients using massively parallel signal sequencing (MPSS). Candidates were additionally subjected to experimental evaluation by semi-quantitat...
Source: Cancer Immunity - June 28, 2008 Category: Cancer & Oncology Authors: Alves PM, Lévy N, Stevenson BJ, Bouzourene H, Theiler G, Bricard G, Viatte S, Ayyoub M, Vuilleumier H, Givel JC, Rimoldi D, Speiser DE, Jongeneel CV, Romero PJ, Lévy F Tags: Cancer Immun Source Type: journals

Dysregulation in immune functions is reflected in tumor cell cytotoxicity by peripheral blood mononuclear cells from head and neck squamous cell carcinoma patients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We assessed the immunological status of stage III and IV head and neck squamous cell carcinoma (HNSCC) patients and age-matched healthy individuals. In HNSCC patients, the total leukocyte count was lower and the proliferating ability of PBMCs against phytohemagglutinin (PHA) was significantly downregulated. These cells showed lower expression of the early activation marker CD69. Within this PBMC population, the proportion of CD4+, CD8+ T cells, CD3- CD56+, CD16+ NK cells and CD3+ CD56+ NK-T cells was seriously downregulated. However, the proportion of CD4+ CD25+ Foxp3+ regulatory T cells having suppressor function was ...
Source: Cancer Immunity - June 13, 2008 Category: Cancer & Oncology Authors: Bose A, Chakraborty T, Chakraborty K, Pal S, Baral R Tags: Cancer Immun Source Type: journals

Concurrent decrease in IL-10 with development of immune-related adverse events in a patient treated with anti-CTLA-4 therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The cytotoxic T lymphocyte antigen-4 (CTLA-4) molecule on T cells acts to maintain homeostasis by regulating the proliferation of recently activated T cells. Blockade of CTLA-4 by anti-CTLA-4 antibody enhances T cell responses and has elicited significant tumor regression in some cancer patients. Clinical trials are ongoing to investigate the efficacy of anti-CTLA-4 antibody as a cancer therapeutic. Reports from several clinical trials have documented the occurrence of adverse events in patients treated with anti-CTLA-4 antibody which have some similarities with autoimmune conditions and have been termed immune-related...
Source: Cancer Immunity - May 28, 2008 Category: Cancer & Oncology Authors: Sun J, Schiffman J, Raghunath A, Ng Tang D, Chen H, Sharma P Tags: Cancer Immun Source Type: journals

Sperm fibrous sheath proteins: a potential new class of target antigens for use in human therapeutic cancer vaccines.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cancer vaccines have been demonstrated to be a promising strategy for treating human neoplastic disease, but one of the limitations of these vaccines remains the paucity of target antigens to which to direct an effective immune response. We hypothesize that sperm fibrous sheath proteins may be a new class of useful antigens for developing successful cancer vaccines. This hypothesis is supported by the expression of two sperm fibrous sheath proteins, called sperm protein 17 and calcium-binding tyrosine-phosphorylation regulated protein, in tumors of unrelated histological origin and their capability to induce T cell-bas...
Source: Cancer Immunity - April 25, 2008 Category: Cancer & Oncology Authors: Chiriva-Internati M, Cobos E, Da Silva DM, Kast WM Tags: Cancer Immun Source Type: journals

Cancer-testis (CT) antigen expression in medulloblastoma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Medulloblastoma is the most common childhood malignant tumor of the central nervous system. Treatment of medulloblastoma requires harmful therapy and nevertheless carries a poor prognosis. Due to their presence in various cancers and their limited expression in normal tissues, CT antigens are ideal vaccine targets for tumor immunotherapy. CT antigens, such as MAGE and NY-ESO-1, have been employed in clinical trials in various malignancies but little is known about their presence in medulloblastoma. We analyzed 25 medulloblastomas for the expression of a panel of CT antigens by RT-PCR and immunohistochemistry. Messenger...
Source: Cancer Immunity - April 23, 2008 Category: Cancer & Oncology Authors: Oba-Shinjo SM, Caballero OL, Jungbluth AA, Rosemberg S, Old LJ, Simpson AJ, Marie SK Tags: Cancer Immun Source Type: journals

An unusual case of metastatic melanoma sensitive to chemotherapy and immunotherapy, with late immune escape in the brain.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 18366150 [PubMed - in process] (Source: Cancer Immunity)
Source: Cancer Immunity - March 28, 2008 Category: Cancer & Oncology Authors: Voelter V, Pica A, Laurent J, Rimoldi D, Bouzourene H, Sajadi A, Matter M, Romero P, Rufer N, Speiser DE Tags: Cancer Immun Source Type: journals

Cancer Vaccines 2007. Cancer and HIV Vaccines: Shared Lessons. October 4-6, 2007, New York, USA. Abstracts.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Authors: PMID: 18363205 [PubMed - indexed for MEDLINE] (Source: Cancer Immunity)
Source: Cancer Immunity - March 26, 2008 Category: Cancer & Oncology Tags: Cancer Immun Source Type: journals

Cancer vaccines: an overview.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The long-held hope that vaccination strategies might be effective against cancer has motivated numerous attempts over the past century to put the idea to test in the clinic. Although the generally disappointing results have cast a long shadow over the field, advances in cancer immunology growing on the remarkable insights from basic immunology provide a strong foundation and powerful new tools to guide current attempts to fashion effective cancer vaccines. This review covers the scientific basis and rationale for cancer vaccines, the challenges involved in assembling the many ingredients going into the construction of ...
Source: Cancer Immunity - March 25, 2008 Category: Cancer & Oncology Authors: Old LJ Tags: Cancer Immun Source Type: journals

Preoperative treatment with a non-steroidal anti-inflammatory drug (NSAID) increases tumor tissue infiltration of seemingly activated immune cells in colorectal cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study evaluates HLA gene expression and tumor infiltration by B-cells, macrophages, dendritic cells, T-helper and cytotoxic T-lymphocytes in response to short-term preoperative treatment with cyclooxygenase inhibitors. Patients with colorectal carcinoma were randomized to receive oral NSAID (indomethacin or celebrex) for three days preoperatively; controls received esomeprazol. Peroperative tumor biopsies and normal colon tissue were analyzed by microarray, quantitative PCR and immunohistochemistry. Efficacy of short-term systemic NSAID treatment was confirmed by measurement of PGE2 production in blood monocytes from ...
Source: Cancer Immunity - March 1, 2008 Category: Cancer & Oncology Authors: Lönnroth C, Andersson M, Arvidsson A, Nordgren S, Brevinge H, Lagerstedt K, Lundholm K Tags: Cancer Immun Source Type: journals

Lung and splenic B cells facilitate diverse effects on in vitro measures of antitumor immune responses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In vitro measures of immune responsiveness toward tumors provide relevant information regarding the prevention and metastatic potential of cancer. In addition, the compartmentalization of immune responses is likely to be an important factor in dictating host antitumor immune responses. We have previously demonstrated that injection of antibody against B cells diminished pulmonary antitumor defenses. In the current study, we determined the effect of B cells on antitumor cellular responses against a lung metastatic tumor, MADB106. Lung B cells displayed sustained surface expression of CD80 and CD86, as compared to spleen...
Source: Cancer Immunity - February 20, 2008 Category: Cancer & Oncology Authors: Jones HP, Wang YC, Aldridge B, Weiss JM Tags: Cancer Immun Source Type: journals

Monoclonal antibody MX35 detects the membrane transporter NaPi2b (SLC34A2) in human carcinomas.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report here that mAb MX35 recognizes the sodium-dependent phosphate transport protein 2b (NaPi2b) in human cancer cells. This conclusion is based on several lines of experimental evidence, including 1) the identification of SLC34A2, the gene coding for NaPi2b, by immunoscreening an ovarian cancer cell line cDNA expression library with mAb MX35; 2) mass spectrometry sequencing of peptides obtained by fragmentation from mAb MX35 affinity-purified antigen, which show complete sequence homology to amino acid sequences in NaPi2b; 3) selective down-regulation of SLC34A2 gene expression by RNA interference and the resulting lo...
Source: Cancer Immunity - February 7, 2008 Category: Cancer & Oncology Authors: Yin BW, Kiyamova R, Chua R, Caballero OL, Gout I, Gryshkova V, Bhaskaran N, Souchelnytskyi S, Hellman U, Filonenko V, Jungbluth AA, Odunsi K, Lloyd KO, Old LJ, Ritter G Tags: Cancer Immun Source Type: journals

Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study aims to analyze the expression of 14 cancer/testis (CT) antigens in multiple myeloma (MM) to identify possible prognostic markers and therapeutic targets. The expression of MAGEA1, MAGEA2, MAGEA3/6, MAGEA4, MAGEA10, MAGEA12, BAGE1, MAGEC1/CT7, the GAGE family, LAGE-1, PRAME, NY-ESO-1, SPA17 and SSX1 was studied by RT-PCR in 15 normal tissues, a pool of 10 normal bone marrow samples, 3 normal tonsils and bone marrow aspirates from 6 normal donors, 3 monoclonal gammopathies of undetermined significance (MGUS), 5 solitary plasmacytomas, 39 MM samples (95% advanced stage) and the MM cell line U266. MAGEC1/CT7 was ex...
Source: Cancer Immunity - February 2, 2008 Category: Cancer & Oncology Authors: Andrade VC, Vettore AL, Felix RS, Almeida MS, Carvalho F, Oliveira JS, Chauffaille ML, Andriolo A, Caballero OL, Zago MA, Colleoni GW Tags: Cancer Immun Source Type: journals

The heterogeneity of the kinetics of response to ipilimumab in metastatic melanoma: patient cases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a negative regulator of T-cell mediated immune responses and is the target of new anti-tumor immunotherapy strategies. Ipilimumab is a fully human, antagonistic monoclonal antibody directed against CTLA-4. Results from preclinical and early clinical trials support current phase II/III testing of ipilimumab as first- and second-line therapy for metastatic melanoma. Ipilimumab promotes durable objective responses and/or stable disease in patients with metastatic melanoma. Adverse events are medically manageable, largely immune-related, and presumably linked to the drug's mecha...
Source: Cancer Immunity - January 18, 2008 Category: Cancer & Oncology Authors: Saenger YM, Wolchok JD Tags: Cancer Immun Source Type: journals

DNA methylation-dependent regulation of BORIS/CTCFL expression in ovarian cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Brother of the Regulator of Imprinted Sites (BORIS/CTCFL) is an autosomal cancer germline (CG) or cancer-testis antigen gene and paralog of CTCF that has been proposed to function as an oncogene in human cancer via dysregulation of the cancer epigenome. Here we show that genetic disruption of DNA methylation in human cancer cells induces BORIS expression, coincident with DNA hypomethylation and an altered histone H3 modification pattern at the BORIS promoter. Rapid amplification of cDNA ends (RACE) mapping revealed that the transcriptional start site of BORIS in human testis, DNMT deficient human cancer cells, and huma...
Source: Cancer Immunity - December 23, 2007 Category: Cancer & Oncology Authors: Woloszynska-Read A, James SR, Link PA, Yu J, Odunsi K, Karpf AR Tags: Cancer Immun Source Type: journals

Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor-associated mesothelin.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Novel therapeutic agents that are safe and effective are needed for the treatment of pancreatic, ovarian, lung adenocarcinomas and mesotheliomas. Mesothelin is a glycosyl-phosphatidyl inositol (GPI)-linked membrane protein of 40 kDa over-expressed in all pancreatic adenocarcinoma and mesothelioma, in >70% of ovarian adenocarcinoma, and in non-small cell lung and colorectal cancers. The biological functions of mesothelin are not known, although it appears to be involved in cell adhesion via its interaction with MUC16. We have recently developed MORAb-009, a mouse-human chimeric IgG1kappa monoclonal antibody with an a...
Source: Cancer Immunity - December 21, 2007 Category: Cancer & Oncology Authors: Hassan R, Ebel W, Routhier EL, Patel R, Kline JB, Zhang J, Chao Q, Jacob S, Turchin H, Gibbs L, Phillips MD, Mudali S, Iacobuzio-Donahue C, Jaffee EM, Moreno M, Pastan I, Sass PM, Nicolaides NC, Grasso L Tags: Cancer Immun Source Type: journals

PLAC1, a trophoblast-specific cell surface protein, is expressed in a range of human tumors and elicits spontaneous antibody responses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Identification of genes that are upregulated in tumors, and whose normal expression excludes adult somatic tissues but includes germline and/or embryonic tissues, has resulted in a rich variety of cancer antigens that are attractive targets for cancer vaccine and other therapeutic approaches. In the present study, we extended this approach to include genes strongly and restrictively expressed in the placenta by mining publicly available SAGE and EST databases. We identified a number of genes with high expression in placenta and different cancer types but with relatively restricted expression in normal tissues. The gene...
Source: Cancer Immunity - November 8, 2007 Category: Cancer & Oncology Authors: Silva WA, Gnjatic S, Ritter E, Chua R, Cohen T, Hsu M, Jungbluth AA, Altorki NK, Chen YT, Old LJ, Simpson AJ, Caballero OL Tags: Cancer Immun Source Type: journals

Cancer is a somatic cell pregnancy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 17983204 [PubMed - in process] (Source: Cancer Immunity)
Source: Cancer Immunity - November 8, 2007 Category: Cancer & Oncology Authors: Old LJ Tags: Cancer Immun Source Type: journals

Upregulation of MICA on high-grade invasive operable breast carcinoma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The MHC class I chain-related gene A (MICA) is frequently expressed on the surface of intestinal epithelium and by many epithelial tumours. MICA is a stress-induced antigen which was identified as an activator of natural killer cells via interaction with the NKG2D receptor. We have raised a rabbit polyclonal antibody against a synthetic peptide that recognises denatured MICA on both Western blots and in formalin-fixed paraffin-embedded sections. In the present study this antibody was used to undertake a definitive study of 530 breast cancer cases with mean follow up of 7 years to determine the prognostic significance o...
Source: Cancer Immunity - October 25, 2007 Category: Cancer & Oncology Authors: Madjd Z, Spendlove I, Moss R, Bevin S, Pinder SE, Watson NF, Ellis I, Durrant LG Tags: Cancer Immun Source Type: journals

LUD 00-009: phase 1 study of intensive course immunization with NY-ESO-1 peptides in HLA-A2 positive patients with NY-ESO-1-expressing cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
NY-ESO-1 is a cancer-testis antigen and an attractive target for immunotherapy in patients with different malignancies. Here we report the results of a phase I clinical study of intensive course NY-ESO-1 peptide vaccination, evaluating the safety, immunogenicity and clinical response in HLA-A2 positive patients with NY-ESO-1 expressing cancers. Of 20 patients enrolled in the trial, 14 completed at least 2 cycles of immunization and were evaluable for clinical and immunological response. Five of these evaluable patients were treated in cohort 1 (baseline seropositive) and 9 patients were treated in cohort 2 (baseline se...
Source: Cancer Immunity - October 20, 2007 Category: Cancer & Oncology Authors: Bender A, Karbach J, Neumann A, Jäger D, Al-Batran SE, Atmaca A, Weidmann E, Biskamp M, Gnjatic S, Pan L, Hoffman E, Old LJ, Knuth A, Jäger E Tags: Cancer Immun Source Type: journals

Expression of cancer-testis (CT) antigens in placenta.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Besides their variable presence in fetal and adult germ cells, CT antigens have occasionally been detected in placental tissue. However, these data are scarce and solely based on mRNA analyses; nothing is known about their presence at the protein level. Here, we analyzed the expression of various CT antigens in placental tissues from gestational age week 5 to week 42 using monoclonal antibodies to various antigens of the MAGE-A and -C families, NY-ESO-1, as well as GAGE. We show that CT antigen expression in placenta varies widely for the various antigens, ranging from completely negative to abundant. Since little is k...
Source: Cancer Immunity - August 25, 2007 Category: Cancer & Oncology Authors: Jungbluth AA, Silva WA, Iversen K, Frosina D, Zaidi B, Coplan K, Eastlake-Wade SK, Castelli SB, Spagnoli GC, Old LJ, Vogel M Tags: Cancer Immun Source Type: journals

A phase I multiple dose, dose escalation study of cG250 monoclonal antibody in patients with advanced renal cell carcinoma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, repeated intravenous doses of up to 50 mg/m(2) of cG250 are safe. Furthermore cG250 has a long half-life and targets clear cell RCC effectively. PMID: 17705349 [PubMed - in process] (Source: Cancer Immunity)
Source: Cancer Immunity - August 22, 2007 Category: Cancer & Oncology Authors: Davis ID, Wiseman GA, Lee FT, Gansen DN, Hopkins W, Papenfuss AT, Liu Z, Moynihan TJ, Croghan GA, Adjei AA, Hoffman EW, Ingle JN, Old LJ, Scott AM Tags: Cancer Immun Source Type: journals

A pilot study of monoclonal antibody cG250 and low dose subcutaneous IL-2 in patients with advanced renal cell carcinoma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, weekly cG250 with daily low-dose subcutaneous IL-2 is well tolerated. IL-2 does not influence cG250 biodistribution or increase HACA. PMID: 17705350 [PubMed - in process] (Source: Cancer Immunity)
Source: Cancer Immunity - August 22, 2007 Category: Cancer & Oncology Authors: Davis ID, Liu Z, Saunders W, Lee FT, Spirkoska V, Hopkins W, Smyth FE, Chong G, Papenfuss AT, Chappell B, Poon A, Saunder TH, Hoffman EW, Old LJ, Scott AM Tags: Cancer Immun Source Type: journals

Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in human glioma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Significant work in animal models combined with compelling studies in human patients together have begun to provide a higher resolution picture of how the immune system regulates cancer development. Currently, this immune system-tumor interaction is represented by the concept of cancer immunoediting, which emphasizes that immunity may subserve either classical cancer immunosurveillance functions or promote the eventual outgrowth of immunoevasive cancer cells. One important line of evidence supporting an immunosurveillance process in humans has been the finding that the presence of distinct profiles of TILs may be corre...
Source: Cancer Immunity - August 20, 2007 Category: Cancer & Oncology Authors: Dunn GP, Dunn IF, Curry WT Tags: Cancer Immun Source Type: journals

Expression of the cancer/testis antigen NY-ESO-1 in primary and metastatic malignant melanoma (MM)--correlation with prognostic factors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, NY-ESO-1 is more frequently expressed in metastatic than in primary MM and its expression is associated with thicker primary lesions and a higher frequency of metastatic disease, indicative of a worse prognosis. Our study suggests that patients with metastatic MM who express NY-ESO-1 may benefit from NY-ESO-1-based immunotherapy. PMID: 17625806 [PubMed - indexed for MEDLINE] (Source: Cancer Immunity)
Source: Cancer Immunity - August 11, 2007 Category: Cancer & Oncology Authors: Velazquez EF, Jungbluth AA, Yancovitz M, Gnjatic S, Adams S, O'Neill D, Zavilevich K, Albukh T, Christos P, Mazumdar M, Pavlick A, Polsky D, Shapiro R, Berman R, Spira J, Busam K, Osman I, Bhardwaj N Tags: Cancer Immun Source Type: journals

Expression of the cancer/testis antigen NY-ESO-1 in primary and metastatic malignant melanoma (MM) - correlation with prognostic factors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, NY-ESO-1 is more frequently expressed in metastatic than in primary MM and its expression is associated with thicker primary lesions and a higher frequency of metastatic disease, indicative of a worse prognosis. Our study suggests that patients with metastatic MM who express NY-ESO-1 may benefit from NY-ESO-1-based immunotherapy. PMID: 17625806 [PubMed - in process] (Source: Cancer Immunity)
Source: Cancer Immunity - July 14, 2007 Category: Cancer & Oncology Authors: Velazquez EF, Jungbluth AA, Yancovitz M, Gnjatic S, Adams S, O'neill D, Zavilevich K, Albukh T, Christos P, Mazumdar M, Pavlick A, Polsky D, Shapiro R, Berman R, Spira J, Busam K, Osman I, Bhardwaj N Tags: Cancer Immun Source Type: journals

Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in human bladder cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The idea of generating cytotoxic T-lymphocytes that have anti-tumor activity has been the focus of many clinical trials aimed at delivering effective immunotherapy to cancer patients. We have gained insight into the human immune system in cancer patients as a result of these numerous clinical investigations. It is now clear that although various vaccination methods are capable of inducing tumor antigen-specific T-cells in the circulating blood, these immunological responses are infrequently correlated with clinical responses. Therefore, it appears that priming of a T-cell response is not sufficient for tumor regression...
Source: Cancer Immunity - June 27, 2007 Category: Cancer & Oncology Authors: Liakou CI, Narayanan S, Ng Tang D, Logothetis CJ, Sharma P Tags: Cancer Immun Source Type: journals

T cell immunomonitoring and tumor responses in patients immunized with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we performed T cell immunomonitoring and analyzed tumor responses in these patients. To evaluate CD4 and CD8 T cell responses, an IFN-gamma secretion assay was used. The assay showed low background and was sensitive for detecting antigen-specific T cells. An increase in the CD4 T cell response was observed in 2 of 2 initially sero-positive and 5 of 7 initially sero-negative patients after vaccination. An increase in the CD8 T cell response was also observed in 2 of 2 sero-positive and 5 of 7 sero-negative patients after vaccination. Analysis of peptides recognized by CD4 and CD8 T cells revealed two dominant...
Source: Cancer Immunity - April 24, 2007 Category: Cancer & Oncology Authors: Uenaka A, Wada H, Isobe M, Saika T, Tsuji K, Sato E, Sato S, Noguchi Y, Kawabata R, Yasuda T, Doki Y, Kumon H, Iwatsuki K, Shiku H, Monden M, Jungbluth AA, Ritter G, Murphy R, Hoffman E, Old LJ, Nakayama E Tags: Cancer Immun Source Type: journals

Increased frequency of regulatory T cells in peripheral blood and tumour infiltrating lymphocytes in colorectal cancer patients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent results have shown a correlation between survival and frequency of tumour infiltrating T lymphocytes in colorectal cancer patients. However, it remains unclear whether the frequency of regulatory T cells is higher in colorectal cancer as compared to normal colon. To address this question we analysed the frequency and function of regulatory T cells in the peripheral blood and tumour infiltrating lymphocytes of colorectal cancer patients. The proportion of regulatory T cells in the peripheral blood of colorectal cancer patients (mean 8%) was significantly higher than that in normal controls (mean 2.2%). There were...
Source: Cancer Immunity - April 18, 2007 Category: Cancer & Oncology Authors: Ling KL, Pratap SE, Bates GJ, Singh B, Mortensen NJ, George BD, Warren BF, Piris J, Roncador G, Fox SB, Banham AH, Cerundolo V Tags: Cancer Immun Source Type: journals

Neem leaf preparation enhances Th1 type immune response and anti-tumor immunity against breast tumor associated antigen.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
An 85-kDa breast tumor associated antigen (BTAA) has been identified and partially characterized from human breast tumors. As BTAA is poorly immunogenic, enhancement of the anti-tumor immunity induced by BTAA is required to obtain an objective clinical response. The potent immune activation by an aqueous preparation of neem (Azadirachta indica) leaf (NLP) suggests its possible utility for enhancing immune responses to tumor vaccines. Mice (Swiss and Balb/c) and rats (Sprague Dawley) immunized with BTAA and NLP have a higher IgG antibody response and a lower IgM response than mice immunized with BTAA alone. Antibody gen...
Source: Cancer Immunity - April 6, 2007 Category: Cancer & Oncology Authors: Mandal-Ghosh I, Chattopadhyay U, Baral R Tags: Cancer Immun Source Type: journals

Identification of XAGE-1 isoforms: predominant expression of XAGE-1b in testis and tumors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we generated a XAGE-1b mAb, USO9-13. The B cell epitope recognized by the USO9-13 mAb was in the C-terminal region of the XAGE-1b protein and is also recognized by sera from patients with lung adenocarcinoma. Using USO9-13 and an anti-Flag mAb, we examined the translation products of the 4 transcripts. The XAGE-1a and b transcripts translated to the XAGE-1b protein. The XAGE-1c transcript possibly translated to 9- and 17-aa polypeptides. The XAGE-1d transcript translated to a protein consisting of 69 amino acids. Immunofluorescence analysis using USO9-13 mAb showed that the XAGE-1b protein is located in the ...
Source: Cancer Immunity - March 12, 2007 Category: Cancer & Oncology Authors: Sato S, Noguchi Y, Ohara N, Uenaka A, Shimono M, Nakagawa K, Koizumi F, Ishida T, Yoshino T, Shiratori Y, Nakayama E Tags: Cancer Immun Source Type: journals

Preclinical evaluation of MORAb-003, a humanized monoclonal antibody antagonizing folate receptor-alpha.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The highly restricted distribution of human folate receptor-alpha (FRalpha) in normal tissues and its high expression in some tumors, along with its putative role in tumor cell transformation, make this antigen a suitable target for antigen-specific, monoclonal antibody-based immunotherapy for oncology indications. We have developed a therapeutic humanized monoclonal antibody with high affinity for FRalpha, named MORAb-003, which was derived from the optimization of the LK26 antibody using a whole cell genetic evolution platform. Here we show that MORAb-003 possesses novel, growth-inhibitory functions on cells overexpr...
Source: Cancer Immunity - March 12, 2007 Category: Cancer & Oncology Authors: Ebel W, Routhier EL, Foley B, Jacob S, McDonough JM, Patel RK, Turchin HA, Chao Q, Kline JB, Old LJ, Phillips MD, Nicolaides NC, Sass PM, Grasso L Tags: Cancer Immun Source Type: journals

Tumor infiltrating lymphocytes: indicators of tumor-related immune responses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 17311362 [PubMed - in process] (Source: Cancer Immunity)
Source: Cancer Immunity - February 25, 2007 Category: Cancer & Oncology Authors: Odunsi K, Old LJ Tags: Cancer Immun Source Type: journals

Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human colorectal cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human colorectal cancer tissues are infiltrated by various immune/inflammatory cells, usually along the invasive margin. These responses tend be regarded as "non-specific". However, it is now clear that these cellular responses, particularly lymphocytic reactions, are independent prognostic factors for a better survival. Immunohistochemical subset analyses have generally disclosed that the number of T-lymphocytes is important. The effects of these T cells tend to be more manifest when the observation periods are longer. These data suggest that some degrees of anti-tumor immunity exist in human colorectal carcinomas. Ho...
Source: Cancer Immunity - February 25, 2007 Category: Cancer & Oncology Authors: Ohtani H Tags: Cancer Immun Source Type: journals