Enhancement of antitumor immune response by targeted interleukin-12 electrogene transfer through antiHER2 single-chain antibody in a murine bladder tumor model

被引：13

作者：

Tsai, Yuh-Shyan ^{[2
,3
,4
]}

Shiau, Ai-Li ^{[1
,2
]}

Chen, Yu-Fon ^{[1
]}

Tsai, Hsin-Tzu ^{[3
,4
]}

Lee, Hwei-Ling ^{[5
]}

Tzai, Tzong-Shin ^{[3
,4
]}

Wu, Chao-Liang ^{[2
,6
]}

机构：

[1] Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, Tainan 70101, Taiwan

[2] Natl Cheng Kung Univ, Coll Med, Inst Clin Med, Tainan 70101, Taiwan

[3] Natl Cheng Kung Univ Hosp, Dept Urol, Coll Med, Tainan 70101, Taiwan

[4] Douliou Branch, Tainan 70101, Taiwan

[5] Natl Cheng Kung Univ, Dept Publ Hlth, Coll Med, Tainan 70101, Taiwan

[6] Natl Cheng Kung Univ, Dept Biochem & Mol Biol, Coll Med, Tainan 70101, Taiwan

来源：

VACCINE | 2009年 / 27卷 / 39期

关键词：

Interleukin-12; HER2; Electrogene transfer; PROVIDE PROGNOSTIC INFORMATION; INVASIVE UROTHELIAL CARCINOMA; TRANSITIONAL-CELL CARCINOMA; GENE AMPLIFICATION; PROTEIN OVEREXPRESSION; FUSION PROTEIN; GAMMA PRODUCTION; IN-VIVO; THERAPY; EXPRESSION;

D O I：

10.1016/j.vaccine.2009.06.079

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5383 / 5392

页数：10