Antitumor immunity induced by VE-cadherin modified DC vaccine
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Jing Zhou1,*, Yufeng Xi2,*, Xiyan Mu3, Rongce Zhao4, Hongdou Chen1, Li Zhang1, Yang Wu2 and Qiu Li1
1The Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Sichuan, China
2State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Sichuan, China
3Department of Gynecology and Obstetrics, Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Sichuan, China
4Division of Liver Transplantation, Department of Liver Surgery, West China Hospital, Sichuan University, Sichuan, China
*These authors have contributed equally to this article
Yang Wu, email: [email protected]
Qiu Li, email: [email protected]
Keywords: DC, VE-cadherin, vaccine, anti-angiogenesis, immunoregulation
Received: March 10, 2017 Accepted: May 23, 2017 Published: June 27, 2017
Dendritic cells (DCs) are the most potent antigen-presenting cells. A strong interest has been developed in DC vaccines for cancer immunotherapy. Besides, angiogenesis is essential for tumor growth. VE-cadherin has a crucial function in various aspects of vascular biological functions. Here, we produced the full VE-cadherin gene modified DC vaccine (DC-VEC). Its antitumor immunity and chief mechanism driving antitumor effect was evaluated. Analyses were performed including test of antitumor antibody, CTL-mediated cytotoxicity experiment, vascular density, evaluation of the variation of cells and cytokines in immunoregulation. Its damage to the major organs was also evaluated. DC-VEC vaccine resulted in retarded tumor progression and prolonged survival in mice. In DC-VEC group, large amount of immunoglobulin was generated, T cells exhibited greater cytotoxicity against VE-cadherin, and tumor angiogenesis was suppressed. Besides, a decrease of VEGF-A and TGF-β1, and an increase of IL-4 and IFN-γ were observed. CD4+ and CD8+ T cells were higher, with increased IFN-γ secretion. The percentage of myeloid-derived suppressor cells and regulatory T cells decreased mildly. Also, it had no pathologic changes in major organs. DC-VEC vaccine represents a promising antitumor immunotherapy. The main mechanism is associated with its anti-angiogenesis and immunoregulation response.
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