title: Anti-tumor angiogenesis effect of genetic fusion vaccine encoding murine beta-defensin 2 and tumor endothelial marker-8 in a CT-26 murine colorectal carcinoma model.
abstract: Tumor endothelial marker 8 (TEM8) is an endothelial-specific marker that is upregulated during tumor angiogenesis. We previously demonstrated that DNA-based vaccine encoding xenogeneic TEM8 can potentiate anti-angiogenesis immunotherapy of malignancy; nevertheless, it remains to be improved in minimizing immune tolerance. Recently, it has been reported that murine beta-defensin 2 (MBD2) is chemotactic for immature dendritic cells and plays a pivotal role in breaking immune tolerance. Herein, we constructed a genetic fusion vaccine encoding murine TEM8 and MBD2 to investigate whether the novel vaccine preferentially elicits therapeutic antitumor immune responses and suppresses cancerous angiogenesis in mouse models. The anti-angiogenesis effect was determined by microvessel density (MVD) using immunohistochemical staining. The efficacy of the fusion vaccine was primarily assessed by detecting cytotoxic T lymphocyte activity ((51)Cr-release assay). Enzyme-linked immunosorbent spot (ELISpot) assay was used to detect TEM8-specific INF-γ production, and the activity of CTL was further verified by a depletion of CD8(+) T cells via anti-CD8 monoclonal antibody. Our results showed that the DNA fusion vaccine possessed an enhanced therapeutic antitumor immunity through anti-angiogenesis in BALB/c mice inoculated with CT26 cells, and this effect was generally attributed to stimulation of an antigen specific CD8(+) T-cell response against mTEM8. In conclusion, our study demonstrated that the fusion vaccine based on mTEM8 and MBD2 induced autoimmunity against endothelial cells, resulting in deceleration of tumor growth, and could be potential therapeutical application in clinic.
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University 30 Gaotanyan Street, Chongqing 400038, China ; Department of Oncology, Peace Hospital of Changzhi Medical College Changzhi 046000, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University 30 Gaotanyan Street, Chongqing 400038, China.
authors.forename: Ganfeng
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University 30 Gaotanyan Street, Chongqing 400038, China.
authors.forename: Peiliang
authors.initials: P
authors.lastname: Geng
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University 30 Gaotanyan Street, Chongqing 400038, China.
authors.forename: Chenhong
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University 30 Gaotanyan Street, Chongqing 400038, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University 30 Gaotanyan Street, Chongqing 400038, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University 30 Gaotanyan Street, Chongqing 400038, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Ruan
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University 30 Gaotanyan Street, Chongqing 400038, China.
authors.forename: Houjie
authors.initials: H
authors.lastname: Liang
keywords: MBD2-mTEM8; anti-tumor effect; fusion vaccine; immunotherapy