title: Local costimulation reinvigorates tumor-specific cytolytic T lymphocytes for experimental therapy in mice with large tumor burdens.
abstract: Cytotoxic T cells recognize tumor Ags and destroy cancer cells in vitro. Adoptive transfer studies with transgenic T cells specific for tumor Ags have demonstrated that CTL are effective only in mice with small tumor burdens and thus appear to have limited potential in cancer immunotherapy. Here we used transgenic mice that express the TCR specific for an unmutated tumor Ag P1A and multiple lineages of P1A-expressing tumors to address this critical issue. We found that local costimulation, either by expression of B7-1 on the tumor cells or by local administration of anti-CD28 mAb 37N, reinvigorated the function of CTL specific for the tumor Ag, as it substantially increased the efficacy of CTL therapy for mice with large tumor burdens. Our study suggests that CTL-based immunotherapy can be manipulated to deal with large tumors.
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, 1645 Neil Avenue, Columbus, OH 43210, USA.
authors.forename: X F
authors.initials: XF
authors.lastname: Bai
authors.forename: J
authors.initials: J
authors.lastname: Bender
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: O
authors.initials: O
authors.lastname: Li
authors.forename: P
authors.initials: P
authors.lastname: Du
authors.forename: P
authors.initials: P
authors.lastname: Zheng
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology*; D018106:CD28 Antigens / Q000276:immunology; D060908:CTLA-4 Antigen; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003601:Cytotoxicity Tests, Immunologic; D018796:Immunoconjugates; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000096:biosynthesis; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D018796:Immunoconjugates; D012333:RNA, Messenger; C076546:tumor rejection antigen P815A, mouse; D000069594:Abatacept