For most human cancers, infectious etiology is unknown and preventative vaccines based on viral antigens, such as HPV for cervical cancer, are not a possibility. However, non-viral cancer-associated antigens, self-antigens abnormally expressed on tumors, have been identified as candidates for vaccines. In patients diagnosed with cancer, preexisting immunity to some of these antigens correlates with better disease outcome or reduced risk of recurrence. In transgenic mice or other animal models where they are expressed as self-antigens, immune responses induced to their tumor forms protect from tumor challenge without causing autoimmunity. Therapeutic vaccines that have utilized these antigens have had only marginal efficacy, which extensive research has now attributed to the presence of many immunosuppressive influences in the tumor microenvironment. MUC1 is one such antigen that has been shown effective as a vaccine in preclinical animal models but has had limited immunogenicity and little efficacy as a therapeutic vaccine in numerous clinical trials in many epithelial tumors, including cancer. Hypothesizing that the major difference between the outcome of the vaccine in preclinical models and in clinical trials is likely to be the high level of immune suppression in cancer patients, we began to develop models and MUC1 vaccines for cancer prevention in patients at risk, before immune suppression develops. We determined first that the tumor form of MUC1 was expressed on early premalignant lesions as well and chose premalignant colonic polyps as the first setting for testing the preventative vaccine. Data will be reviewed from a published feasibility study confirming immunogenicity and safety of the MUC1 vaccine in healthy individuals at risk for colon cancer. Data will then be presented from a recently completed unpublished randomized, double blind placebo controlled multi-center prophylactic MUC1 vaccine trial in the same patient population, those with a history of advanced colonic polyps and therefore at increased risk of developing colon cancer.
Citation Format: Olivera (Olja) J. Finn. Tumor-associated antigen MUC1 vaccine for colon cancer prevention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY17-03.