title: HOCl oxidation-modified CT26 cell vaccine inhibits colon tumor growth in a mouse model.
abstract: Despite progress in elucidating mechanisms associated with colorectal cancer and improvement of treatment methods, it remains a frequent cause of death worldwide. New and more effective therapies are therefore urgently needed. Recent studies have shown that immunogenicity of whole ovarian tumor cells and subsequent T cell response were potentiated by oxidation modification with hypochlorous acid (HOCl) in vitro and ex vivo. These results prompted us to investigate the protective antitumor response with an HOCl treated CT26 colorectal cancer cell vaccine in an in vivo mouse model. Administration of HOCl modified vaccine triggered robust antitumor immunity to autologous tumor cells in mice and prolonged survival period significantly. In addition, increased necrosis and apoptosis were found in tumor tissue from the oxidation group. Interestingly, ELISPOT assays showed that specific T cell responses were not elicited in response to the immunizing cellular antigen, in contrast to raising sera antibody titer and antibody binding activity shown by ELISA assay and flow cytometry. Further evaluation of the mechanisms underlying HOCl modified vaccine mediated humoral immunity highlighted the role of antibody-dependent cell-mediated cytotoxicity. These results combined with previous studies suggest that HOCl oxidation modified whole cell vaccine has wide applicability as a cancer vaccine because it can target both T cell- and B cell-specific responses. It may thus represent a promising approach for the immunotherapy of colorectal cancer.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Huang
authors.forename: Cong
authors.initials: C
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yu-Qin
authors.initials: YQ
authors.lastname: Yao
authors.forename: Yu-Xi
authors.initials: YX
authors.lastname: Wang
authors.forename: Lan-Tu
authors.initials: LT
authors.lastname: Gou
authors.forename: Chen
authors.initials: C
authors.lastname: Yi
authors.forename: Jin-Liang
authors.initials: JL
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D017209:Apoptosis; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006997:Hypochlorous Acid / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D016877:Oxidants / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D019496:Cancer Vaccines; D016877:Oxidants; D012333:RNA, Messenger; D006997:Hypochlorous Acid