Novel protein‐based vaccine against self‐antigen reduces the formation of sporadic colon adenomas in mice

Novel immunopreventive strategies are emerging that show great promise for conferring long‐term protection to individuals at high risk of developing colorectal cancer. The KISIMA vaccine platform utilizes a chimeric protein comprising: 1) a selected tumor antigen; 2) a cell‐penetrat-ing peptide to improve antigen delivery and epitope presentation, and 3) a TLR2/4 agonist to serve as a self‐adjuvant. This study examines the ability of a KISIMA vaccine against achaete‐scute family bHLH transcription factor 2 (Ascl2), an early colon cancer antigen, to reduce colon tumor formation by stimulating an anti‐tumor immune response. Vaccine administrations were well‐tolerated and led to circulating antibodies and antigen‐specific T cells in a mouse model of colorectal cancer. To assess preventive efficacy, the vaccine was administered to mice either alone or in combination with the immune checkpoint inhibitor anti‐PD‐1. When delivered to animals prior to colon tumor for-mation, the combination strategy significantly reduced the development of colon microadenomas and adenomas, as compared to vehicle‐treated controls. This response was accompanied by an in-crease in the intraepithelial density of CD3+ T lymphocytes. Together, these data indicate that the KISIMA‐Ascl2 vaccine shows great potential to be a safe and potent immunopreventive intervention for individuals at high risk of developing colorectal cancer.