Prophylactic cancer vaccination by targeting functional non-self.

Despite the monumental success of childhood prophylactic vaccination, there is no similar program designed to provide protection as we age against adult onset diseases like breast cancer. Instead, the predominant focus of current cancer vaccine strategy is to vaccinate after the tumors become established. This strategy has at best provided incremental improvement in overall survival. We propose the development of an adult vaccination program modeled on the childhood program that provides protection against diseases we confront as we enter our middle age. Since most cases of adult cancers are not associated with definitive etiopathogenic viruses, we propose extending our selection of vaccine targets to tissue-specific self proteins that are over-expressed in developing tumors but are no longer expressed in normal tissues ('retired or former self'), are expressed in normal tissues under readily avoidable conditions ('conditional self'), or are incapable of targeting any clinically significant autoimmune complications ('irrelevant self'). By extending prophylactic vaccination to such "functional non-self" targets, prophylactic vaccination against adult onset diseases like breast cancer may occur safely in the absence of any autoimmune inflammatory complications and may potentially reduce disease incidence in a manner that mimics the impact of childhood vaccination on diseases like measles and polio.