Identification of Tumor Rejection Antigens for Breast Cancer Using a Mouse Tumor Rejection Model

摘要

Pre-menopausal patients whose breast cancers are, in general, estrogen receptor (ER) negative and biologically more aggressive, are particularly in need of novel therapeutic interventions. A breast cancer vaccine to prevent relapse after conventional treatment would be of enormous clinical value. Several cancer vaccine studies have demonstrated that breast cancer patients can develop tumor antigen specific immune responses after a vaccine is given. Most of these approaches target a single immunogenic protein or antigen thus limiting the vaccine to those patients whose tumor expresses that antigen. We propose the development of a multi-antigen vaccine that could potentially benefit any ER negative breast cancer patient; the category of patient at highest risk of relapse. Several high throughput antigen discovery tools have been developed that have greatly helped the identification of immunogenic proteins in breast cancer patients. One such technique, SEREX (serological analysis of cDNA expression libraries) identifies tumor antigens based on spontaneous antibody immunity that can occur in breast cancer patients. To date, over 2,000 tumor antigens have been identified from a variety of cancers using SEREX. In fact, so many tumor antigens have been identified a major question facing tumor immunologists today is- which antigen will induce anti-tumor immunity. Investigators evaluating immunity to leukemia have recently utilized patients who develop an anti-tumor response after immunotherapy to identify true 'tumor rejection' antigens, that is, those immunogenic proteins which, if targeted, would induce an anti-tumor response. This work was possible because one of the treatments of relapsed leukemia is immunotherapy using donor lymphocyte infusions. The investigators could identify which immunogenic proteins were associated with the development of a remission after immunotherapy.