T cell-mediated suppression of angiogenesis results in tumor protective immunity.
Antiangiogenic intervention is known to inhibit tumor growth and dissemination by attacking the tumor's vascular supply. Here, we report that this was achieved for the first time using an oral DNA minigene vaccine against murine vascular endothelial growth factor receptor 2 (FLK-1), a self-antigen overexpressed on proliferating endothelial cells in the tumor vasculature. Moreover, we identified the first H-2Db-restricted epitope, FLK400 (VILT-NPISM), specifically recognized by cytotoxic T lymphocytes (CTLs). Such CTLs were capable of killing FLK-1+ endothelial cells, resulting in suppression of angiogenesis and long-lived tumor protection. The specificity of this immune response was indicated because the DNA vaccine encoding the entire FLK-1 gene also induced a FLK400-specific CTL response. This minigene vaccine strategy provides a more flexible alternative to whole-gene vaccination and facilitates in-depth mechanism studies to tailor DNA vaccines for optimal T-cell activation and tumor protection.
Zhou
He
H
Department of Immunology, The Scripps Research Institute, R218, IMM13, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Luo
Yunping
Y
Mizutani
Masato
M
Mizutani
Noriko
N
Reisfeld
Ralph A
RA
Xiang
Rong
R
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007109:Immunity; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
D000951:Antigens, Neoplasm; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D019444:Vaccines, DNA; D040301:Vascular Endothelial Growth Factor Receptor-2