title: T cell-mediated suppression of angiogenesis results in tumor protective immunity.
abstract: 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.
authors.affiliation: Department of Immunology, The Scripps Research Institute, R218, IMM13, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA.
authors.forename: He
authors.initials: H
authors.lastname: Zhou
authors.forename: Yunping
authors.initials: Y
authors.lastname: Luo
authors.forename: Masato
authors.initials: M
authors.lastname: Mizutani
authors.forename: Noriko
authors.initials: N
authors.lastname: Mizutani
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Reisfeld
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
mesh_terms: 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
chemical_list: D000951:Antigens, Neoplasm; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D019444:Vaccines, DNA; D040301:Vascular Endothelial Growth Factor Receptor-2