Orally administered DNA vaccine delivery by attenuated Salmonella typhimurium targeting fetal liver kinase 1 inhibits murine Lewis lung carcinoma growth and metastasis.
The vascular endothelial growth factor (VEGF) receptor 2 (VEGFR-2), also called fetal liver kinase 1 (FLK1) in mice and kinase insert domain receptor (KDR) in humans, is an endothelial cell specific receptor tyrosine kinase that mediates lung cancer angiogenesis. We hypothesized that an active immunotherapy approach targeting FLK1 may inhibit lung cancer growth and metastasis. To test this hypothesis, we evaluated whether immune responses to FLK1 could be elicited in mice by immunization with an orally administered DNA vaccine encoding the extracellular domain (ECD) of FLK1 (pcDNA3.1-FLK1(ECD)) carried by attenuated Salmonella typhimurium. We found that the vaccine was effective at protective antitumor immunity in Lewis lung carcinoma models in mice by breaking immune tolerance to FLK1 self-antigen. Both FLK1-specific humoral and cellular immune responses against endothelial cells can be induced in mice by immunization with pcDNA3.1-FLK1(ECD). Immunization with pcDNA3.1-FLK1(ECD) resulted in tumor suppression and prolonged survival in mice challenged with Lewis lung carcinomas cells. Experimental pulmonary metastases were strongly inhibited in pcDNA3.1-FLK1(ECD) immunized mice challenged with Lewis lung carcinoma cells. Thus, we conclude that the plasmid DNA vaccine encoding the extracellular domain of FLK1 could be an important component of FLK1 DNA vaccine to prevent lung carcinoma recurrence and metastasis after surgery.
Zuo
Shu Guang
SG
Tumor Institute of Yunnan Province, the Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), No. 519 Kunzhou Road, Kunming, Yunnan 650118, P. R. China.
Chen
Yan
Y
Wu
Zhi Ping
ZP
Liu
Xin
X
Liu
Chun
C
Zhou
Yong Chun
YC
Wu
Cui Ling
CL
Jin
Cong Guo
CG
Gu
Yu Lan
YL
Li
Jia
J
Chen
Xiao Qun
XQ
Li
Yong
Y
Wei
Hui Ping
HP
Li
Li Hua
LH
Wang
Xi Cai
XC
D000284:Administration, Oral; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D018827:Carcinoma, Lewis Lung / Q000201:enzymology / Q000473:pathology* / Q000517:prevention & control* / Q000556:secondary; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D018014:Gene Transfer Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D012486:Salmonella typhimurium / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000276:immunology
D001428:Bacterial Vaccines; D019496:Cancer Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D040301:Vascular Endothelial Growth Factor Receptor-2