MHC class II-restricted tumor antigens recognized by CD4+ T cells: new strategies for cancer vaccine design.
The adoptive transfer of tumor-infiltrating lymphocytes (TIL) can mediate tumor regression in patients with melanoma. This finding has led to the identification and characterization of tumor-associated antigens recognized by CD8+ TIL. Several clinical trials based on the genes recognized by these CD8+ T cells have been attempted, but with only limited success. Meanwhile, increasing evidence has demonstrated that CD4+ T cells play important roles in generating and maintaining antitumor immune responses in animal models. These data suggest that it may be necessary to engage both CD4+ and CD8+ T cells for more effective antitumor immunotherapy. In this report, we review emerging molecular approaches in cloning major histocompatibility complex (MHC) class II restricted tumor antigens recognized by CD4+ T cells as well as approaches to identify new MHC class II-restricted epitopes from known tumor antigens recognized by CD8+ cytotoxic T lymphocytes and/or antibodies. Progress made in this field has shed light on the roles of tumor antigen-specific CD4+ T cells in humans; it has also provided new insights into the understanding of tumor genesis and the interaction between tumor and the immune system. More importantly, the discovery of MHC class II-restricted tumor antigens has provided opportunities for developing a new generation of cancer vaccines aimed at eliciting both CD4+ and CD8+ T-cell responses against tumor.
Zeng
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Surgery Branch, National Cancer Institute National Institutes of Health, Bethesda, Maryland 20892, USA.
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D015195:Drug Design; D000949:Histocompatibility Antigens Class II; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008969:Molecular Sequence Data; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000949:Histocompatibility Antigens Class II