[The antiangiogenic effect of DNA vaccine based on beta-defensin 2 fused with VE-cadherin].
OBJECTIVE
To explore the feasibility of generating beta defensin 2 fusion vaccine to break the immune tolerance of self antigens associated with angiogenesis.


METHODS
PCR amplification of mature beta defensin 2 (Def) and extracelluar segment of Vascular Endothelial Cadherin (Cad) was conducted. (GGGS)3 was used as linker peptide for fusion plasmid(Def-Cad). All the three segments were inserted into pSecTag2B plasmid (pSec), and CT26 tumor cells were transfected. Expression was verified by RT-PCR and chemotaxis assay. The alginate bead model was used to study the antiangiogenic effect of fusion plasmid vaccination.


RESULTS
All constructions were verified by sequencing and were found expressed in mammalian cell. The beta defensin 2 fusion protein had similar capacity to chemoattract dendritic cells as compared with nonfusion protein (P>0.05). The alginate bead assay revealed that the tumor-induced angiogenesis in fusion plasmid immunized mice was significantly suppressed when compared with that in nonfusion plasmid (P<0.01).


CONCLUSIONS
An active immunization strategy based on beta defensin 2 fused with angiogenesis related antigen of endothelial can inhibit angiogenesis and may be a useful approach for cancer therapy.
Wang
Guo-qing
GQ
State Key Laboratory of Biotherapy, Cancer center, West China Hospital, Sichuan University, Chengdu 610041, China.
Wang
Yong-sheng
YS
Wang
Rui
R
Wu
Yang
Y
Du
Xiao-bo
XB
Xu
Jian-Rong
JR
Diao
Peng
P
D020533:Angiogenesis Inhibitors / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D001483:Base Sequence; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000098:blood supply; D009389:Neovascularization, Pathologic / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology; D023083:beta-Defensins / Q000096:biosynthesis / Q000235:genetics*; D000099152:Cadherin 5
D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; D015820:Cadherins; D019496:Cancer Vaccines; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D023083:beta-Defensins; D000099152:Cadherin 5