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Antigen-specific therapies in multiple sclerosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Multiple sclerosis is the major neurological disease of young adults in the western world, affecting about 1 per 1,000. It is characterised by chronic or recurrent lesions of inflammatory damage in the white matter of the central nervous system. Within such lesions, the protective myelin sheath is stripped off axons by infiltrated macrophages which leads to impaired conductivity. The inflammatory process most likely starts by activation of helper T cells directed against local myelin antigens. Currently, efforts are directed at specifically blocking such myelin-reactive helper T cells in order to co...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Heat shock proteins and the antitumor T cell responseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Heat shock proteins (HSP) have been shown to participate in the antitumor T cell response. First, HSP play a crucial role in the intracellular pathway for antigen processing where HSP can make complexes with a broad spectrum of cellular proteins and peptides through their chaperone functions. In this pathway, macrophages are required for processing the chaperoned peptides to make stable molecules with the major histocompatibility complex (MHC) class I molecules, even when HSP-peptide complexes are exogenously administered. Through this pathway, vaccination with HSP-peptide complexes is thus able to ...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

PrefaceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content TypeJournal Article JournalBiotherapyOnline ISSN 1573-8280Print ISSN 0921-299X Journal VolumeVolume 10 Journal IssueVolume 10, Number 3 / March, 1998
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

The expression of potency of neutralizing antibodies for interferons and other cytokinesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The occurrence of antibody formation in patients administered biologically active human proteins as biotherapy for different diseases emphasizes the importance of establishing a common method of reporting neutralizing antibody levels for such cytokines. For quantitative neutralization bioassays, the preferred expression of the neutralizing potency of an antiserum is a titer, that is, the dilution of serum that reduces 10 Laboratory Units (LU)/ml of the cytokine to 1 Laboratory Unit/ml, the endpoint of most bioassays. This 10-to-1 LU/ml expression, which has been recommended by the World Health Organ...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Heat shock proteins as potential targets in the therapy of inflammatory arthritisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Whether heat shock proteins (hsp) will be therapeutic targets in arthritis depends on their role in pathogenesis. In this article, three possibilities are considered. Firstly, an excessive immune response to bacterial hsp could be arthritogenic — as may occur in reactive arthritis. In these circumstances therapy would be directed to down-regulating this immune response, or altering the nature of the immune response e.g. by changing cytokine production from interferon-g to IL-4. However this approach depends on the immune response to bacterial hsp not being critical for control of the bacterial inf...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Oral administration of HSP-containing E.Coli extract OM-89 has suppressive effects in autoimmunity. Regulation of autoimmune processes by modulating peripheral immunity towards hsp’s?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract OM-89 (Subreum) is anE. coli extract used for oral administration in the treatment of rheumatoid arthritis. It contains bacterial heat shock proteins, namely hsp60 and hsp70, which were shown to be major immunogenic constitutents of the drug. Immunity to bacterial heat-shock antigens was shown to be a means of immunomodulation of (experimental) autoimmune disease and possibly inflammation in general. This was demonstrated for mycobacterial hsp60 respectively hsp70 in autoimmune disease models for arthritis, diabetes and encephalitis. Parallel to the effects displayed by immunisation with hsp, oral a...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Mucosal modulation of immune responses to heat shock proteins in autoimmune arthritisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Induction of oral tolerance to antigens that are targets of self-reactive immune responses is an attractive approach to antigen-specific immune therapy of autoimmune diseases. Oral tolerization has indeed proven to be safe and effective in amelioration of autoimmune diseases in animal models. In humans, results have been somewhat controversial. The emphasis given to clinical outcome rather than to immunomodulation, and the difficulty in identifying appropriate candidate antigens contribute to the controversy. Heat shock proteins are promising targets for immune intervention. Immune reactivity to hea...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Nasal administration of arthritis-related T cell epitopes of heat shock protein 60 as a promising way for immunotherapy in chronic arthritisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Adjuvant Arthritis (AA) can be induced in Lewis rats by immunisation with mycobacterial antigens. The disease can be passively transferred with T cell clone A2b, which recognises the 180–188 amino acid sequence in mycobacterial heat shock protein 60 (hsp60) and which crossreacts with crude cartilage proteoglycans. We succeeded to induce peripheral tolerance to this AA-associated T cell epitope following nasal administration of a peptide containing this epitope (mycobacterial hsp60 176–190). In rats treated nasally with 176–190 and immunised with mycobacterial hsp60, proliferative responses to ...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

HLA-DR/DQ Transgenic, class II deficient mice as a novel model to select for HSP T cell epitopes with immunotherapeutic or preventative vaccine potentialEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Protective immunity against mycobacteria is dependent on antigen/MHC class II specific, CD4+ Th1 cells. HLA-DR3-restricted Th1 cells respond to a subset of mycobacterial antigens, including the immunodominant hsp65, and recognize a single epitope in hsp65, notably p1-20. Altered peptide ligands (APL) of p1-20 can inhibit p1-20/hsp65-induced proliferation of DR3-restricted T cells in an allele specific mannerin vitro. In order to develop a preclinical model in which p1-20 APL can be testedin vivo in the context of HLA, we have used murine class II deficient, HLA transgenic (Ab0) mice, in which all CD4+...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Immune responses to stress proteins: Applications to infectious disease and cancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Heat shock proteins, or stress proteins have been identified as part of a highly conserved cellular defence mechanism mediated by multiple, distinct gene familes and corresponding gene products. As intracellular chaperones, stress proteins participate in many essential biochemical pathways of protein maturation and function active during times of stress and during normal cellular homeostasis. In addition to their well-characterized role as protein chaperones, stress proteins are now realized to possess another important biological property: immunogenicity. Stress proteins are now understood to play ...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Structure-activity of type I interferonsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Type I IFNs constitute a family of proteins exhibiting high homology in primary, secondary, and tertiary structures. They interact with the same receptor and transmit signals to cellular nucleus through a similar mechanism, eliciting roughly homogeneous biological activity. Nevertheless, the members of that family, IFNα species, IFNβ and IFNω, due to local differences in the structure sometime show distinct properties. From the reported data it results that even minute changes or differences in the primary sequences could be responsible for a significant variety of biological actions, thus induci...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Measurement of cytokine antibodies. Test developmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Several assays have been used for detection of antibodies against cytokines. The choice of assay is greatly dependent on the intended goal, e.g. detection of naturally occurring antibodies or therapy induced antibodies. The different assays can be grouped in 2 categories. The interference or indirect assays are based on the detection of the test sample interference with the biological activity, with detection of the cytokine in EIA or with binding to cellular receptors. In direct assays cytokine antibodies are detected by binding to solid phase fixed cytokines, followed by incubation with a secondar...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Potential therapeutic use of antibodies directed towards HuIFN-γEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract IFN-γ is an important regulator of immune responses and inflammation. Studies in animal models of inflammation, autoimmunity, cancer, transplant rejection and delayed-type hypersensitivity have indicated that administration of antibodies against IFN-γ can prevent the occurrence of diseases or alleviate disease manifestations. Therefore, it is speculated that such antibodies may have therapeutical efficacy in human diseases. Since animal-derived antibodies are immunogenic in patients several strategies are being developed in order to reduce or abolish this human anti-mouse antibody (HAMA) response....
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Natural antibodies to interferon-gammaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Natural antibodies to interferon (IFN)-γ were detected in the serum of virus-infected patients and also, at a low titre, in the serum of healthy subjects. The increased titre of antibodies to IFN-γ in the sera of virus-infected patients, and its decrease with clinical resolution, indicate that these antibodies are related to viral infection and probably reflect IFN-γ production as a result of antigenic stimulationin vivo. Natural antibodies to IFN-γ were affinity purified and studied for their capability to interferein vitro with the multiple activities of the lymphokine. Data obtained show that ...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Anti-cytokine autoantibodies: Epiphenomenon or critical modulators of cytokine actionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Low amounts of high-affinity autoantibodies to various cytokines have been detected in sera from healthy donors. Their levels, although highly variable, are increased in the circulation of patients subjected to cytokine therapy or suffering from a variety of immunoinflammatory diseases. It has been suggested that these autoantibodies play a regulatory role in the intensity and duration of an immune response. The antibodies may prevent the binding of a cytokine to its specific cell surface receptor thereby neutralizing its biological activityin vivo. They may also act as carrier proteins preventing t...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Natural antibodies to IL-2Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Natural antibodies to human interleukin-2 are present in sera of patients infected with human immunodeficiency virus and also, at a lower titre, in sera of healthy individuals. These antibodies could be purified by affinity-chromatography. Purified human anti-hIL-2 antibodies can interfere with lymphocyte proliferation both in the lymphokine activated killer cell assay and in the mixed lymphocyte culture. The neutralizing activity observedin vitro suggests that these antibodies play a role in the elaborate cytokine network by which the immune system regulates its response. Content TypeJournal Arti...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Interferon antibodies in patients with infectious diseasesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Interferons (IFNs) are generally recognized as the most important therapeutic agent in some infectious diseases such as chronic hepatitis B and C. Since the early clinical trials it was documented that the therapeutic use of IFNs could be complicated by the development of antibodies able to neutralize or to bind to the IFN molecule. After several years of research it is now widely accepted that the presence of circulating anti-IFN antibodies may affect the response to IFN. Here we summarize what is currently know on the clinical significance of antibodies to IFN in IFN-treated viral disease...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

The incidence and clinical significance of antibodies to interferon-a in patients with solid tumorsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract It is well known that natural and recombinant proteins can cause antibody formation in the host. We have studied the incidence of binding and neutralizing antibodies in carcinoid patients (n=327). All together 204 patients received interferon-α 2b (Intron-A), median does 15 MU range 9–35 MU/week subcutaneously and 51% of the patients developed binding antibodies by immunoassay and 17% showed positive neutralization assay but high titer antibodies (>800 NU/ml) were only found in 4% of the patients. The median time until the development of binding antibodies was 26 months and neutralizing antibo...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Treatment-induced antibodies to interleukin-2Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Interleukin-2 (IL-2) is a 15 kDa glycoprotein with proven activity as an immune stimulant in the treatment of malignant disorders, congenital and acquired immune deficiencies, infectious disorders, and as an adjuvant to vaccines. Both natural and recombinant type IL-2 preparations have been applied in clinical treatment trials and have turned out to be immunogenic, although to a varying extent. Enzyme immunoassays and western blotting are standard procedures for the detection of IL-2-binding antibodies, whereas the neutralizing capacity of these antibodies is frequently demonstrated by inhibition of...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

In vivo and in vitro effects of sizofiran on the human neutrophils and the serum opsonic activityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract In this paper, we examine the effects of SPG, which is a well known BRM, both in vivo and in vitro on the neutrophilic ROS production and the serum opsonic activity by the chemiluminescence technique using luminol as a probe. To investigate the in vivo effects, SPG was administered to 12 healthy male volunteers and two phases of enhancement of the neutrophilic ROS production and the serum opsonic activity were observed. In vitro, the addition of SPG showed a dose-dependent suppression. To investigate the mechanisms in these contradictory effects of SPG, supernatants of a lymphocytes culture medium...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Treatment of head and neck cancers with BRMsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract It has been reported that immunologic function is deteriorated in head and neck cancer patients by primary therapies such as surgery, irradiation and chemotherapy or tumor itself. As previously described by us, immunologic dysfunction in such patients may be recovered by treatment with BRMs. In the present study, we investigated the effects of BRMs on survival of patients who had primarily been treated in our clinic. Fifty-one patients (23 patients; Stage I or Stage II, 28 patients; Stage III or Stage IV) were treated with BRMs (BRM group), and 49 patients (22 patients; Stage I or Stage II, 27 pa...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Long-term treatment with recombinant interferon alpha-2b prolongs survival of asymptomatic HIV-infected individualsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusion: IFN alpha treatment given from the early stages of infection, but not after the appearance of AIDS symptoms, can prolong survival. Content TypeJournal Article JournalBiotherapyOnline ISSN 1573-8280Print ISSN 0921-299X Journal VolumeVolume 10 Journal IssueVolume 10, Number 2 / June, 1997
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

The in vitro effect of new muramyl peptide derivatives on cytotoxic activity of NK (Natural Killer) cells from hamsters bearing AB Bomirski MelanomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The modulation of NK activity by muramyl dipeptides derivatives against Ab (amelanotic) Bomirski melanoma and human erythroleukemia K562 cells was studied in vitro. The stimulatory effect was observed for 3 of 7 muramyl dipeptides: MDP(L-Ala)C921, MDPC857 and L18-MDP(Ala) in relation to cytotoxic activity of NK cells obtained from peripheral blood and spleen of healthy and Ab Bomirski melanoma bearing hamsters. An increased of cytotoxic activity NK cells isolated from animals before and during the transplantable phase of the tumor against K562 was found. A similar stimulation was received for NK cel...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Augumentation of splenic antitumor immunity by local immunotherapy in gastric cancer patientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract We previously reported that the antitumor effect of OK-432, a streptococcal preparation, was markedly augmented when this agent was injected into tumors together with fibrinogen. In order to elucidate the effect of this treatment on the spleen, we assessed splenic function in gastric cancer patients receiving preoperative local immunotherapy with OK-432 and fibrinogen. Immunohistochemical studies of the spleen at 7 days after intratumoral injection therapy revealed numerous macrophages phagocytizing OK-432 in the splenic sinuses. Phenotypic analysis of splenocytes by flow cytometry revealed an incre...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Mpl ligand or thrombopoietin: Biological activitiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Thrombopoietin (TPO) or Mpl ligand is the primary physiological regulator of platelet production. This cytokine is the most potent stimulator of the proliferation and differentiation of MK progenitor and precursor cellsin vitro. It also acts additively or synergistically with several cytokines on progenitor cells from various hematopoietic lineages, including the primitive stem cells. The factor is an extremely potent thrombocytopoietic agent when administrated to normal animals, and it accelerates platelet and erythropoietic recovery in several models of myelosuppression. Phase I/II clinical trials...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Hematopoietic growth factors in autologous transplantationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Hematopoietic growth factors (HGFs) sustain the survival, proliferation and differentiation of hematopoietic stem cells and some functions of mature blood cells. In man several HGFs have been characterised and cloned so far, and this has allowed investigators to confer the rationale for the clinical application of these molecules in hematology and oncology. In particular G-CSF and GM-CSF are currently utilised to abrogate the hematological toxicity of chemotherapy for standard and dose-intensified therapy, neutropenia following bone marrow and peripheral blood stem cell transplantation. Moreover the...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

Natural and therapeutically-induced antibodies to cytokinesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Serum samples obtained from non-immunocompromised patients treated therapeutically with recombinant cytokines (e.g. Il-1α; Il-1β; Il-2 to Il-18; IFNα; GM-CSF; G-CSF; etc.) often reveal the presence of high affinity anti-cytokine antibodies. Antibody Fab binding in a saturable manner by ELISA and RIA or western immunoblotting prove their specificity. Antibody level often increases in these patients with repeated cytokine administration, suggesting boosts of antigen stimulation. However, the appearance in circulation of auto-antibodies to exogenous cytokine is not always associated with a decreased ...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

ForewordEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content TypeJournal Article JournalBiotherapyOnline ISSN 1573-8280Print ISSN 0921-299X Journal VolumeVolume 10 Journal IssueVolume 10, Number 4 / December, 1998
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals

The role of homeobox genes in hematopoiesisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Homeobox genes encode transcription factors containing a common DNA-binding motif found in virtually all animal species. Different homeobox gene families have evolved which encode homeodomains of different types or classes and thus far approximately 170 homeobox genes have been cloned. Homeoproteins are involved in the control of animal development and several lines of evidence strongly suggest that they may contribute to the regulation of hematopoiesis. Many members of this large family are expressed in blood cells. Moreover, homeobox containing genes have been involved in translocation events occu...
Source: Biotherapy - July 19, 2007 Category: Biomedical Science Tags: Biotherapy Source Type: journals