MHC Class II–Restricted Tumor Antigens Recognized by CD4+ T Cells: New Strategies for Cancer Vaccine Design

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Abstract
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.