Immunity against tumor angiogenesis induced by a fusion vaccine with murine beta-defensin 2 and mFlk-1.
OBJECTIVE
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 beta-defensin 2 (MBD2) protein to induce both humoral and cellular immunity against mFlk-1, with the targeting especially focused on immature dendritic cells.


METHODS
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.


CONCLUSIONS
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.
Wang
Yong-sheng
YS
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Guo Xue Xiang No. 37, Chengdu, Sichuan, People's Republic of China.
Wang
Guo-qing
GQ
Wen
Yan-jun
YJ
Wang
Lian
L
Chen
Xian-cheng
XC
Chen
Ping
P
Kan
Bin
B
Li
Jiong
J
Huang
Canhua
C
Lu
You
Y
Zhou
Qin
Q
Xu
Ning
N
Li
Dan
D
Fan
Ling-yu
LY
Yi
Tao
T
Wu
Hong-bo
HB
Wei
Yu-quan
YQ
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000098:blood supply* / Q000276:immunology / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000517:prevention & control*; D010455:Peptides / Q000235:genetics / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology* / Q000627:therapeutic use; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000276:immunology; D023083:beta-Defensins / Q000235:genetics* / Q000276:immunology
D001323:Autoantibodies; D019496:Cancer Vaccines; C117047:Defb2 protein, mouse; D010455:Peptides; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D023083:beta-Defensins; C526111:pMBD2-mFlk-1 vaccine; D040301:Vascular Endothelial Growth Factor Receptor-2