title: Enhancement of antitumor immune response by targeted interleukin-12 electrogene transfer through antiHER2 single-chain antibody in a murine bladder tumor model.
abstract: Interleukin-12 (IL-12), despite exerting antitumor activity, has limited therapeutic uses due to its systemic toxicity. Since HER2 (also known as ErbB-2, neu, and HER2/neu) is frequently overexpressed on cancer cells, HER2-targeted delivery of IL-12 to tumors may be a promising strategy for enhancing antitumor immunity. Here we showed that intramuscular electrogene transfer of an expression vector encoding a fusion protein antiHER2scFv-IL12, which consists of antiHER2 single-chain variable fragment (scFv) and single-chain IL-12, significantly retarded tumor growth and prolonged the survival in a syngeneic bladder tumor model. Elevated IL-12 and interferon-gamma (IFN-gamma) levels, increased infiltration of CD4(+) and CD8(+) T cells, and reduced vascular endothelial growth factor (VEGF) expression in the tumors, as well as enhanced cytolytic activity of splenocytes were noted in the treated mice. Our results suggest that this approach may be effective for the treatment of HER2-overexpressing tumors.
authors: Institute of Clinical Medicine, National Cheng Kung University Medical College, Tainan, Taiwan.
authors: Yuh-Shyan
authors: YS
authors: Tsai
authors: Ai-Li
authors: AL
authors: Shiau
authors: Yu-Fon
authors: YF
authors: Chen
authors: Hsin-Tzu
authors: HT
authors: Tsai
authors: Hwei-Ling
authors: HL
authors: Lee
authors: Tzong-Shin
authors: TS
authors: Tzai
authors: Chao-Liang
authors: CL
authors: Wu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology / Q000276:immunology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D007135:Immunoglobulin Variable Region; D007371:Interferon-gamma; D018664:Interleukin-12; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C508053:ERBB2 protein, human