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Immunity against Tumor Angiogenesis Induced by a Fusion Vaccine with Murine ß-Defensin 2 and mFlk-1

Authors' Affiliations: ¹ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and ² Department of Gynecology and Obstetrics, Second West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China

Requests for reprints: Yu-quan Wei, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Guo Xue Xiang, No. 37, Chengdu, Sichuan 610041, People's Republic of China. Phone/Fax: 86-28-85501675; E-mail: Hyuquawei{at}vip.sina.comH.

Purpose: Previous studies indicated that humoral or cellular immunity against murine vascular endothelial growth factor 2 (mFlk-1) was elicited to inhibit tumor growth. Here we describe a genetic fusion vaccine, pMBD2-mFlk-1, based on the targeting of a modified mFlk-1 to antigen-presenting cells by a murine ß-defensin 2 (MBD2) protein to induce both humoral and cellular immunity against mFlk-1, with the targeting especially focused on immature dendritic cells.

Experimental Design: The protective and therapeutic antitumor immunity of the fusion vaccine was investigated in mouse models. Antiangiogenesis effect was detected by immunohistochemical staining and alginate-encapsulate tumor cell assay. The mechanisms of the fusion vaccine were primarily explored by detection of autoantibodies and CTL activity and confirmed by the deletion of immune cell subsets.

Results: The fusion vaccine elicited a strong protective and therapeutic antitumor immunity through antiangiogenesis in mouse models, and this worked through stimulation of an antigen-specific CD8⁺ T-cell response as well as a specific B-cell response against mFlk-1. The findings were confirmed by depletion of immune cell subsets and in knockout mice.

Conclusion: Our study showed that a fusion vaccine based on self immune peptide (MBD2) and self antigen (mFlk-1) induced autoimmunity against endothelial cells, resulting in inhibition of tumor growth, and could be further exploited in clinical applications of cancer immunotherapy.