title: Orally administered DNA vaccine delivery by attenuated Salmonella typhimurium targeting fetal liver kinase 1 inhibits murine Lewis lung carcinoma growth and metastasis.
abstract: 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.
authors.affiliation: 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.
authors.forename: Shu Guang
authors.initials: SG
authors.lastname: Zuo
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhi Ping
authors.initials: ZP
authors.lastname: Wu
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Chun
authors.initials: C
authors.lastname: Liu
authors.forename: Yong Chun
authors.initials: YC
authors.lastname: Zhou
authors.forename: Cui Ling
authors.initials: CL
authors.lastname: Wu
authors.forename: Cong Guo
authors.initials: CG
authors.lastname: Jin
authors.forename: Yu Lan
authors.initials: YL
authors.lastname: Gu
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Xiao Qun
authors.initials: XQ
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Hui Ping
authors.initials: HP
authors.lastname: Wei
authors.forename: Li Hua
authors.initials: LH
authors.lastname: Li
authors.forename: Xi Cai
authors.initials: XC
authors.lastname: Wang
mesh_terms: 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
chemical_list: D001428:Bacterial Vaccines; D019496:Cancer Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D040301:Vascular Endothelial Growth Factor Receptor-2