Peptide and Protein Vaccines for Cancer

The immune surveillance theory, first proposed by Frank Burnet and Lewis Thomas in the 1950s, hypothesizes that the immune system specifically recognizes and destroys transformed cells [1]. Although debate regarding the relevance of immunity in cancer has persisted over the last half century, the discovery of tumor antigens recognized by T cells provides clear evidence that cellular and serologic immune responses against tumors do exist. Studies in animals have established an important role for both innate and adaptive immunity in tumor rejection and modulation of tumor growth. T cells appear to be critical mediators of adaptive immunity against antigen-expressing tumor cells. Tumor-infiltrating lymphocytes (TILs) isolated from melanoma lesions can recognize autologous and human leukocyte antigen (HLA)matched tumor cells in vitro [2, 3]. Furthermore, T cell reactivity against tumor antigens can often be identified in the peripheral blood of cancer patients and healthy donors. Advances in our understanding of antigen presentation and T cell activation have provided the foundation for rationally-designed immunotherapy strategies that induce anti-tumor immune responses in cancer patients while limiting toxicity. Many of these have shown efficacy in animal models. However, peptideand proteinbased vaccine clinical trials, and clinical trials of adoptive T cell transfer, have thus far been promising but have not demonstrated consistent clinical benefit.