title: T/Tn immunotherapy avoiding immune deviation.
abstract: Tumor immunotherapy, capable of inducing both cellular and humoral immune responses, is an attractive treatment strategy for cancer. It has been reported that the inactivation of cell-mediated immunity by hyper-activation of humoral immunity-referred to as immune deviation-does not inhibit tumor growth. We investigated the ability of several adjuvants to elicit Thomsen-Friedenreich (T/Tn)-specific humoral immunity while avoiding immune deviation and conferring protection against tumorigenesis. T/Tn (9:1) antigen was purified from blood type O erythrocytes donated by healthy Korean volunteers. Immunization was performed using T/Tn only, T/Tn mixed with Freund's adjuvant (T/Tn+FA), keyhole limpet hemocyanin (KLH)-conjugated T/Tn mixed with FA (KLH-T/Tn+FA), or oxidized mannan-conjugated T/Tn mixed with FA (ox-M-T/Tn+FA). Anti-T/Tn antibodies were generated in the T/Tn+FA, KLH-T/Tn+FA, and ox-M-T/Tn+FA groups. The antibody level was highest in the KLH-T/Tn+FA group. Mice immunized with ox-M-T/Tn+FA showed specific complement-dependent cytotoxicity, and were protected against T/Tn-positive mammary adenocarcinoma cell challenge, although anti-T/Tn antibody levels were the highest in the KLH-T/Tn+FA group. These results demonstrate that an ox-M-conjugated T/Tn vaccine mixed with FA can promote cellular immunity while moderating the humoral immune response, thereby effectively inhibiting tumor growth.
authors.affiliation: Tumor Immunity Medical Research Center, Cancer Research Institute, Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hye-Youn
authors.initials: HY
authors.lastname: Son
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, VIC, Australia.
authors.forename: Vasso
authors.initials: V
authors.lastname: Apostolopoulos
authors.affiliation: Tumor Immunity Medical Research Center, Cancer Research Institute, Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea cwkim@snu.ac.kr.
authors.forename: Chul-Woo
authors.initials: CW
authors.lastname: Kim
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000818:Animals; D000906:Antibodies / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D008297:Male; D051379:Mice; D008875:Middle Aged
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D015295:Antigens, Tumor-Associated, Carbohydrate; C040286:Tn antigen; C025991:Thomsen-Friedenreich antibodies; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin
keywords: T/Tn cancer vaccine; oxidized mannan; tumor immunotherapy