Preventing cancer by targeting abnormally expressed self-antigens: MUC1 vaccines for prevention of epithelial adenocarcinomas

Abstract

Prophylactic vaccines based on tumor-associated antigens (TAAs) have elicited concerns due to their potential toxicity. Because TAAs are considered self-antigens, the prediction is that such vaccines will induce autoimmunity. While this has been observed in melanoma, where an antitumor immune response leads to vitiligo, autoimmunity has almost never been seen following vaccination with numerous other TAAs. We hypothesized that antigen choice determines outcome and have been working to identify TAAs whose expression differs between normal and tumor tissue, and thus could elicit antitumor immunity without autoimmunity. Studies on the epithelial TAA MUC1 have revealed that, compared to MUC1 on normal cells, tumors, premalignant lesions, and noncancerous pathologies affecting epithelial cells express abnormal MUC1, which is not a self-antigen but rather an abnormal disease-associated antigen (DAA). This distinction, which can be made for many known TAAs, has broad implications for the design and acceptance of preventative cancer vaccines.