Targeting "Retired Antigens" for Cancer Immunoprevention.

Identification of immune targets for cancer immunoprevention, or immunotherapy, has historically focused on tumor-associated (self) antigens or neoantigens expressed on malignant cells. For self-antigens, overcoming tolerance can be a difficult challenge. Neoantigens do not suffer from this limitation, but the lack of recurrent mutations yielding common neoantigens that can be exploited in vaccines is a problem for many tumor types. Targeting "retired antigens," a specialized type of self-antigen, may have considerable advantages. Antigens no longer expressed in mature or aged individuals should pose reduced risk of autoimmune sequelae. Indeed, self-tolerance of these antigens may have naturally faded. Thus, when the retired antigens are highly expressed in cancer cells, it may be easier to overcome the remaining tolerance. Women who are BRCA1/2 carriers may be among the first to benefit as candidate retired antigens have been identified as highly expressed in ovarian and breast cancer cells. Although there is good preclinical data supporting this immune targeting concept, additional research is needed to understand the underlying immune phenomena and optimize the vaccine strategy. .