Improving immunotherapy by conditionally enhancing MHC class I presentation of tumor antigen-derived peptide epitopes

Tumors represent an "altered" self cell type that can be recognized by both the host humoral (B cells, antibodies) and cellular (T cells) adaptive immune systems. "Because most known tumor-associated antigens (TAA) recognized by T cells represent overexpressed or aberrantly expressed proteins, which are not mutated and to which tolerance has been developed, the anti-TAA T-cell repertoire available to the cancer patient is of moderate-to-low avidity. Specific vaccinations typically amplify the absolute number of such T cells, but may have little consequence on improving their functional avidity, which may fall below a critical threshold required for effective recognition of tumor cells in situ. This review will discuss methods to improve low-avidity T-cell recognition of cancer cells by manipulating the tumor cells themselves to conditionally express higher levels of TAA-derived peptide epitopes presented in major histocompatibility (MHC) complexes. This may facilitate the design and performance of novel combinational therapies for the effective treatment of a broad range of cancer types.