Inhibition of tumor growth with a vaccine based on xenogeneic homologous fibroblast growth factor receptor-1 in mice.
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.
He
Qiu-ming
QM
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.
Wei
Yu-quan
YQ
Tian
Ling
L
Zhao
Xia
X
Su
Jing-mei
JM
Yang
Li
L
Lu
You
Y
Kan
Bin
B
Lou
Yan-yan
YY
Huang
Mei-juan
MJ
Xiao
Fei
F
Liu
Ji-yan
JY
Hu
Bing
B
Luo
Feng
F
Jiang
Yu
Y
Wen
Yan-jun
YJ
Deng
Hong-xin
HX
Li
Jiong
J
Niu
Tin
T
Yang
Jin-liang
JL
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
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