Immunity against tumor angiogenesis induced by a fusion vaccine with murine β-defensin 2 andmFlk-1

Abstract

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 bya murine β-defensin 2 (MBD2) protein to induce both humoral and cellular immunitya gainst mFlk-1, with the targeting especially focused on immature dendritic cells. Experimental Design: The protective and therapeutic antitumor immunityof 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 primarilyex plored by detection of autoantibodies and CTL activity and confirmed by the deletionof 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 studys howed 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. ©2007 American Association for Cancer Research.