FLK-1-based minigene vaccines induce T cell-mediated suppression of angiogenesis and tumor protective immunity in syngeneic BALB/c mice.
Angiogenesis is a rate-limiting step in the development of tumors. Here, we demonstrate that oral minigene DNA vaccines against murine vascular endothelial growth factor receptor-2 (FLK-1), a self-antigen overexpressed on proliferating endothelial cells in the tumor vasculature, induced protection against tumors of different origin in syngeneic BALB/c mice. This protection is mediated by CD8 T cells, which specifically kill FLK-1(+) endothelial cells, resulting in marked suppression of tumor angiogenesis. More importantly, the minigene vaccine proved to be of similar efficacy as a vaccine encoding the whole FLK-1 gene. These data suggest a FLK-1 minigene vaccine provides a more flexible alternative to the whole gene vaccine and will facilitate their future design and clinical applications in cancer therapy and prevention.
Luo
Yunping
Y
Department of Immunology, The Scripps Research Institute, R218, IMM13, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Markowitz
Dorothy
D
Xiang
Rong
R
Zhou
He
H
Reisfeld
Ralph A
RA
D000284:Administration, Oral; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000098:blood supply / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000628:therapy; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000276:immunology*
D019496:Cancer Vaccines; D019444:Vaccines, DNA; D040301:Vascular Endothelial Growth Factor Receptor-2