MHC class II-transfected tumor cells directly present antigen to tumor-specific CD4+ T lymphocytes.
We have developed and shown to be efficacious an immunotherapeutic strategy to enhance the generation of tumor-specific CD4+ T helper lymphocytes. The approach uses autologous tumor cells genetically modified to express syngeneic MHC class II genes as cell-based immunogens and is based on the hypothesis that tumor cells directly present tumor Ags to CD4+ T cells. Since the conventional pathway for CD4+ T cell activation is indirect via professional APC, induction of immunity following immunization with class II-transfected tumor cells was examined in bone marrow chimeric mice. Both tumor and host-derived cells are APC for tumor Ags, suggesting that the efficacy of tumor cell vaccines can be significantly improved by genetic modifications that enhance tumor cell Ag presentation.
Armstrong
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Department of Biology, University of Maryland, Baltimore 21250, USA.
Clements
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Ostrand-Rosenberg
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D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D005838:Genotype; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology; D012513:Sarcoma, Experimental / Q000235:genetics* / Q000276:immunology*; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014162:Transfection / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D009113:Muramidase