title: Inhibition of tumor growth with a vaccine based on xenogeneic homologous fibroblast growth factor receptor-1 in mice.
abstract: Angiogenesis is important for the growth of solid tumors. The breaking of the immune tolerance against the molecule associated with angiogenesis should be a useful approach for cancer therapy. However, the immunity to self-molecules is difficult to elicit by a vaccine based on autologous or syngeneic molecules due to immune tolerance. Basic fibroblast growth factor (bFGF) is a specific and potent angiogenic factor implicated in tumor growth. The biological activity of bFGF is mediated through interaction with its high-affinity receptor, fibroblast growth factor receptor-1 (FGFR-1). In this study, we selected Xenopus FGFR-1 as a model antigen by the breaking of immune tolerance to explore the feasibility of cancer therapy in murine tumor models. We show here that vaccination with Xenopus FGFR-1 (pxFR1) is effective at antitumor immunity in three murine models. FGFR-1-specific autoantibodies in sera of pxFR1-immunized mice could be found in Western blotting analysis. The purified immunoglobulins were effective at the inhibition of endothelial cell proliferation in vitro and at the antitumor activity in vivo. The antitumor activity and production of FGFR-1-specific autoantibodies could be abrogated by depletion of CD4+ T lymphocytes. Histological examination revealed that the autoantibody was deposited on the endothelial cells within tumor tissues from pxFR1-immunized mice, and intratumoral angiogenesis was significantly suppressed. Furthermore, the inhibition of angiogenesis could also be found in alginate-encapsulate tumor cell assay. These observations may provide a new vaccine strategy for cancer therapy through the induction of autoimmunity against FGFR-1 associated with angiogenesis in a cross-reaction.
authors.affiliation: Key Laboratory of Biotherapy of Human Diseases, Ministry of Education, People's Republic of China and Cancer Center, West China Hospital, Guo Xue Xiang No. 37, Sichuan 610041, People's Republic of China.
authors.forename: Qiu-ming
authors.initials: QM
authors.lastname: He
authors.forename: Yu-quan
authors.initials: YQ
authors.lastname: Wei
authors.forename: Ling
authors.initials: L
authors.lastname: Tian
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Jing-mei
authors.initials: JM
authors.lastname: Su
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: You
authors.initials: Y
authors.lastname: Lu
authors.forename: Bin
authors.initials: B
authors.lastname: Kan
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Lou
authors.forename: Mei-juan
authors.initials: MJ
authors.lastname: Huang
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.forename: Ji-yan
authors.initials: JY
authors.lastname: Liu
authors.forename: Bing
authors.initials: B
authors.lastname: Hu
authors.forename: Feng
authors.initials: F
authors.lastname: Luo
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yan-jun
authors.initials: YJ
authors.lastname: Wen
authors.forename: Hong-xin
authors.initials: HX
authors.lastname: Deng
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
authors.forename: Tin
authors.initials: T
authors.lastname: Niu
authors.forename: Jin-liang
authors.initials: JL
authors.lastname: Yang
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019496:Cancer Vaccines; D002455:Cell Division; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000737:chemistry / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D007136:Immunoglobulins / Q000737:chemistry; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D009389:Neovascularization, Pathologic; D010957:Plasmids / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D014981:Xenopus
chemical_list: D000464:Alginates; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D018076:DNA, Complementary; D007136:Immunoglobulins; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1