HOCl Oxidation-modified CT26 Cell Vaccine Inhibits Colon Tumor Growth in a Mouse Model

Despite progress in elucidating mechanisms associated with colorectal cancer and improvement of treatmentmethods, it remains a frequent cause of death worldwide. New and more effective therapies are therefore urgentlyneeded. Recent studies have shown that immunogenicity of whole ovarian tumor cells and subsequent T cellresponse were potentiated by oxidation modification with hypochlorous acid (HOCl) in vitro and ex vivo. Theseresults prompted us to investigate the protective antitumor response with an HOCl treated CT26 colorectal cancercell vaccine in an in vivo mouse model. Administration of HOCl modified vaccine triggered robust antitumorimmunity to autologous tumor cells in mice and prolonged survival period significantly. In addition, increasednecrosis and apoptosis were found in tumor tissue from the oxidation group. Interestingly, ELISPOT assaysshowed that specific T cell responses were not elicited in response to the immunizing cellular antigen, in contrastto raising sera antibody titer and antibody binding activity shown by ELISA assay and flow cytometry. Furtherevaluation of the mechanisms underlying HOCl modified vaccine mediated humoral immunity highlighted therole of antibody-dependent cell-mediated cytotoxicity. These results combined with previous studies suggestthat HOCl oxidation modified whole cell vaccine has wide applicability as a cancer vaccine because it can targetboth T cell- and B cell-specific responses. It may thus represent a promising approach for the immunotherapyof colorectal cancer.