Peptide vaccines prevent tumor growth by stimulating a similar T cell repertoire as the native tumor antigen (165.46)

Abstract

Abstract A major goal of immunotherapy for cancer is to focus and activate the T cell response to tumor-associated antigens. One strategy to stimulate these T cells is to immunize with specific peptides in combination immunostimulatory modalities. We are using an immunogenic mouse colon cancer model to characterize both the activating peptides and the responding T cells. We have identified peptides that interact with the restricting MHC molecule and a tumor-specific T cell clone that are either non-protective like the natural antigen, or protective against tumor challenge. The T cell repertoires responding to these peptides and the tumor are distinct, although they overlap with the natural antigen. Examination of the Vb regions expressed by the tumor-specific T cells, showed that the responses to the peptide variants were more focused than those to the natural antigen. Further ex vivo analysis showed that the T cells responding to the protective peptides and in the TIL (tumor infiltrating lymphocytes) were selected to express a CDR3b motif, which was also shared by the T cells responding to the natural antigen. We suggest that the increased signal delivered by the peptide variants that target the T cells naturally responding to the tumor such as those found in TIL result in more effective antitumor responses.