Retired self-proteins as vaccine targets for primary immunoprevention of adult-onset cancers.

We propose that optimized control of adult-onset cancers requires the incorporation of a defense-based strategy in the form of preemptive immunity induced in healthy cancer-free subjects prior to the appearance of tumors. However, development of such prophylactic immunity has traditionally targeted etiopathogenic agents. We propose that in the absence of available cancer-inducing pathogens, safe and effective protection against the emergence of tumors may be achieved by inducing targeted immunity against tissue-specific self-proteins that are 'retired' from expression at immunogenic levels in normal tissues due to the normal aging process, but are expressed in emerging tumors. Thus, 'retired' self-proteins may substitute for unavailable pathogens as targets for developing prophylactic immunity against tumors we confront with age like breast, ovarian and prostate cancer. Our current efforts involve testing this primary 'immunoprevention' strategy in clinical trials focused on prevention of the more aggressive and lethal forms of breast cancer.