Insights on peptide vaccines in cancer immunotherapy

Abstract

Human tumor-associated antigens are generally weakly immunogenic and therefore able to escape detection by the immune system. Numerous studies have shown, however, that immune cells infi ltrate many tumors, and that these cells are vital for keeping tumor burden in check. Immunotherapy can enhance this process by further stimulating tumor-recognizing cells while decreasing the function of immunosuppressive cells, such as regulatory T cells and myeloid-derived suppressor cells, thereby creating a more immune-activating tumor microenvironment. Peptide vaccines can stimulate and activate T cells specifi c to tumor-associated antigens. Because peptides endogenously expressed by tumor cells are often weak immunogens, researchers are investigating various strategies for making them more immunogenic and more potent as vaccines. Here we review multiple strategies for enhancing peptide immunogenicity, including (a) peptides with amino acid substitutions at anchor residues and heteroclitic analogs, (b) multiple variance long peptides, (c) whole protein and 15-mer overlapping peptides, (d) multiple peptides recognizing different tumor-associated antigens, (e) class I and II epitope hybrid vaccines, (f) peptide-pulsed dendritic cells, and (g) combining peptide vaccines with other therapies. While it is unlikely that peptide vaccines alone could signifi cantly affect progressive disease, the combination of these vaccines with the right adjuvants and/or immunomodulatory agents has shown promising results in clinical trials.