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Immunotherapeutic Strategies (immunotherapeutic + strategy)
Selected AbstractsExpression of melanoma-associated antigens in melanoma cell culturesEXPERIMENTAL DERMATOLOGY, Issue 7 2005Mirjana Urosevic Abstract:, The efficiency of melanoma immunotherapy appears to depend on both melanoma- and immune system-specific factors. Melanoma-specific factors include melanoma-associated antigen (MAA) expression as well as HLA class I molecule expression. We investigated the expression of five MAA , Melan-A/MART-1, tyrosinase, gp100, MAGE-1 and MAGE-3 , by means of FACS analysis in 50 melanoma cell cultures and compared them to the cultures of human foreskin-derived melanocytes and melanoma cell line UKRV-Mel2. Melan-A, tyrosinase and gp100 expression was frequently reduced in melanoma cell cultures, compared to that in foreskin melanocytes, whereas MAGE-1 and MAGE-3 expression showed variable degree of upregulation, compared to that in foreskin melanocytes. The expression of all tested MAA demonstrated high interindividual variability. We further show that cell cultures derived from the same tissue sample are oligoclonal in nature, by demonstrating the presence of up to three cell populations bearing distinct MAA profile. Analysing samples derived from the same patient but each at a different time point, we show that MAA expression profile changes over time either in positive (increase) or in negative (decrease) direction. Finally, we demonstrate that brain metastasis-derived cell cultures significantly overexpress Melan-A and MAGE-3, compared to primary tumours and other metastatic sites (P -value range: 0.05,0.001). Elucidation of the MAA expression patterns and the kinetics within the same patient as well as during the course of the disease may help improve current and develop new immunotherapeutic strategies. [source] Immunomodulatory therapy for chronic hepatitis B virus infectionFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2005D. Sprengers Abstract Hepatitis B virus (HBV) is one of the most prevalent viral pathogens of man with around 350 million chronically infected patients. It has been postulated that in persistently infected individuals the HBV-specific immune response is too weak to eliminate HBV from all infected hepatocytes, but sufficiently strong to continuously destroy HBV-infected hepatocytes and to induce chronic inflammatory liver disease. The primary aim in the treatment of chronic hepatitis B is to induce sustained disease remission and prevent serious complications like liver failure and/or hepatocellular carcinoma. The recent emergence of drug-resistant HBV mutants and post-treatment relapse as a consequence of nucleoside analogue monotherapy emphasizes that the principal goal should be to stimulate a successful immune response. In this paper we will focus on the immune response to HBV and we will review reported data on immunotherapeutic strategies like immunomodulatory drugs (cytokines and Thymic derivates) and vaccine therapies using currently available recombinant anti-HBV vaccines, lipopeptide-based T cell vaccine and newly developed genetic vaccines. [source] Dendritic cell-based human immunodeficiency virus vaccineJOURNAL OF INTERNAL MEDICINE, Issue 1 2009C. R. Rinaldo Abstract. Dendritic cells (DC) have profound abilities to induce and coordinate T-cell immunity. This makes them ideal biological agents for use in immunotherapeutic strategies to augment T-cell immunity to HIV infection. Current clinical trials are administering DC-HIV antigen preparations carried out ex vivo as proof of principle that DC immunotherapy is safe and efficacious in HIV-infected patients. These trials are largely dependent on preclinical studies that will provide knowledge and guidance about the types of DC, form of HIV antigen, method of DC maturation, route of DC administration, measures of anti-HIV immune function and ultimately control of HIV replication. Additionally, promising immunotherapy approaches are being developed based on targeting of DC with HIV antigens in vivo. The objective is to define a safe and effective strategy for enhancing control of HIV infection in patients undergoing antiretroviral therapy. [source] Crystallization and preliminary X-ray diffraction analysis of the Fab fragment of WO2, an antibody specific for the A, peptides associated with Alzheimer's diseaseACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 5 2008Kwok S. Wun The murine monoclonal antibody WO2 specifically binds the N-terminal region of the amyloid , peptide (A,) associated with Alzheimer's disease. This region of A, has been shown to be the immunodominant B-cell epitope of the peptide and hence is considered to be a basis for the development of immunotherapeutic strategies against this prevalent cause of dementia. Structural studies have been undertaken in order to characterize the molecular basis for antibody recognition of this important epitope. Here, details of the crystallization and X-ray analysis of the Fab fragment of the unliganded WO2 antibody in two crystal forms and of the complexes that it forms with the truncated A, peptides A,1,16 and A,1,28 are presented. These crystals were all obtained using the hanging-drop vapour-diffusion method at 295,K. Crystals of WO2 Fab were grown in polyethylene glycol solutions containing ZnSO4; they belonged to the orthorhombic space group P212121 and diffracted to 1.6,Å resolution. The complexes of WO2 Fab with either A,1,16 or A,1,28 were cocrystallized from polyethylene glycol solutions. These two complex crystals grew in the same space group, P212121, and diffracted to 1.6,Å resolution. A second crystal form of WO2 Fab was grown in the presence of the sparingly soluble A,1,42 in PEG 550 MME. This second form belonged to space group P21 and diffracted to 1.9,Å resolution. [source] Either interleukin-12 or interferon-, can correct the dendritic cell defect induced by transforming growth factor ,1 in patients with myelomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2004Ross Brown Summary The poor response to immunotherapy in patients with multiple myeloma (MM) indicates that a better understanding of any defects in the immune response in these patients is required before effective therapeutic strategies can be developed. Recently we reported that high potency (CMRF44+) dendritic cells (DC) in the peripheral blood of patients with MM failed to significantly up-regulate the expression of the B7 co-stimulatory molecules, CD80 and CD86, in response to an appropriate signal from soluble trimeric human CD40 ligand. This defect was caused by transforming growth factor ,1 (TGF,1) and interleukin (IL)-10, produced by malignant plasma cells, and the defect was neutralized in vitro with anti-TGF,1. As this defect could impact on immunotherapeutic strategies and may be a major cause of the failure of recent trials, it was important to identify a more clinically useful agent that could correct the defect in vivo. In this study of 59 MM patients, the relative and absolute numbers of blood DC were only significantly decreased in patients with stage III disease and CD80 up-regulation was reduced in both stage I and stage III. It was demonstrated that both IL-12 and interferon- , neutralized the failure to stimulate CD80 up-regulation by huCD40LT in vitro. IL-12 did not cause a change in the distribution of DC subsets that were predominantly myeloid (CD11c+ and CDw123,) suggesting that there would be a predominantly T-helper cell type response. The addition of IL-12 or interferon- , to future immunotherapy trials involving these patients should be considered. [source] The immunotherapeutic potential of dendritic cells in type 1 diabetesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2010G. Mukherjee Summary Type 1 diabetes is an autoimmune disease characterized by destruction of the pancreatic islet beta cells that is mediated primarily by T cells specific for beta cell antigens. Insulin administration prolongs the life of affected individuals, but often fails to prevent the serious complications that decrease quality of life and result in significant morbidity and mortality. Thus, new strategies for the prevention and treatment of this disease are warranted. Given the important role of dendritic cells (DCs) in the establishment of peripheral T cell tolerance, DC-based strategies are a rational and exciting avenue of exploration. DCs employ a diverse arsenal to maintain tolerance, including the induction of T cell deletion or anergy and the generation and expansion of regulatory T cell populations. Here we review DC-based immunotherapeutic approaches to type 1 diabetes, most of which have been employed in non-obese diabetic (NOD) mice or other murine models of the disease. These strategies include administration of in vitro -generated DCs, deliberate exposure of DCs to antigens before transfer and the targeting of antigens to DCs in vivo. Although remarkable results have often been obtained in these model systems, the challenge now is to translate DC-based immunotherapeutic strategies to humans, while at the same time minimizing the potential for global immunosuppression or exacerbation of autoimmune responses. In this review, we have devoted considerable attention to antigen-specific DC-based approaches, as results from murine models suggest that they have the potential to result in regulatory T cell populations capable of both preventing and reversing type 1 diabetes. [source] Photodynamic therapy-generated tumor cell lysates with CpG-oligodeoxynucleotide enhance immunotherapy efficacy in human papillomavirus 16 (E6/E7) immortalized tumor cellsCANCER SCIENCE, Issue 5 2007Su-Mi Bae Immunotherapy with photodynamic therapy (PDT) offers great promise as a new alternative for cancer treatment; however, its use remains experimental. In this study, we examined the immunotherapeutic significance of human papillomavirus (HPV)-immortalized tumor cell lysates induced by PDT with CpG-oligodeoxynucleotide (ODN). PDT-cell lysates were generated by irradiating Radachlorin (5 µg/mL) preloaded TC-1 cells carrying HPV 16 E7. PDT-cell lysates plus ODN coinjection for protection against E7-expressing tumors as well as specific immune responses were evaluated with the following tests: heat shock protein 70 (HSP70) enzyme-linked immunosorbent assay, in vitro and in vivo tumor growth inhibition, interferon-, (IFN-,) and tumor necrosis factor-, (TNF-,) assay, cytotoxic T-lymphocyte assay, and fluorescence activated cell sorting (FACS) analysis. PDT-cell lysates plus ODN coinjection showed a significant suppression of tumor growth at both prophylactic and therapeutic levels, compared to PDT (or F/T)-cell lysates or ODN alone. In addition, we evaluated the level of the immune response with the coinjection. HSP70, an important regulator of inflammatory and immune response, was observed in abundance in the PDT-cell lysates. IFN-, production and cytotoxic T lymphocytes (CTL) responses were induced by PDT-cell lysates plus ODN injection. The coinjection resulted in PDT-cell lysate-specific antibodies (IgG1, IgG2a, IgG2b, and IgG3) and T-helper cell responses significantly higher than PDT-cell lysates alone. Moreover, IFN-, production and CTL responses were significantly induced in the PDT-cell lysate plus ODN immunized groups. These enhanced immune responses appeared to be mediated by CD8+ T cells only. These data suggest that PDT-cell lysates plus ODN injection may be an effective approach to induce CTL immune responses as a possible immunotherapeutic strategy for cancer therapy. (Cancer Sci 2007; 98: 747,752) [source] | ||||||||||