title: Combination gene therapy with CD86 and the MHC class II transactivator in the control of lung tumor growth.
abstract: Early reports suggest that the costimulatory molecule CD86 (B7-2) has sporadic efficacy in tumor immunity, whereas changes in cancer immunity mediated by the MHC class II transactivator (CIITA) have not been extensively investigated. CIITA activates MHC class II expression in most cells; however, in the Line 1 lung carcinoma model system, CIITA activates MHC class I and well as class II. Here we show that CD86 is very effective in inducing a primary immune response against Line 1. Tumor cells expressing CD86 grew in only 50% of the mice injected with live cells, and those mice that developed tumors did so with significantly delayed kinetics. Furthermore, irradiated CD86-expressing Line 1 cells served as an effective tumor vaccine, demonstrating that CD86 is effective in inducing tumor immunity in the Line 1 system. These data suggest that if CIITA and CD86 cooperate, enhanced tumor immunity could be achieved. CIITA alone was mildly beneficial in slowing primary tumor growth but only when expressed at low levels. Clones expressing high levels of class II MHC grew as fast as or faster than parental tumor, and CIITA expression in a tumor vaccine assay lacked efficacy. When CIITA and CD86 were coexpressed, there was no cooperative immune protection from tumor growth. Cells that coexpress both genes also failed as a cancer vaccine, suggesting a negative role for CIITA in this lung carcinoma. These data suggest that human cancer vaccine trials utilizing CIITA gene therapy alone or in combination with CD86 should be approached with caution.
authors.affiliation: Lineberger Comprehensive Cancer Center, Department of Microbiology-Immunology, University of North Carolina at Chapel Hill 27599, USA.
authors.forename: B K
authors.initials: BK
authors.lastname: Martin
authors.forename: J G
authors.initials: JG
authors.lastname: Frelinger
authors.forename: J P
authors.initials: JP
authors.lastname: Ting
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D051940:B7-2 Antigen; D019496:Cancer Vaccines / Q000276:immunology; D002277:Carcinoma / Q000235:genetics / Q000276:immunology; D004357:Drug Synergism; D005802:Genes, MHC Class II / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods*; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins; D015534:Trans-Activators / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D019496:Cancer Vaccines; C497965:Cd86 protein, mouse; D006131:Growth Inhibitors; C083728:MHC class II transactivator protein; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D015534:Trans-Activators