Immunotherapy of tumors with protein vaccine based on chicken homologous Tie-2.
OBJECTIVE
Tie-2 is an endothelium-specific receptor tyrosine kinase known to play a key role in tumor angiogenesis. The present study explores the feasibility of immunotherapy of tumors by using a protein vaccine based on chicken Tie-2 as a model antigen to break the immune tolerance against Tie-2 in a cross-reaction between the xenogeneic homologous and self-Tie-2.


RESULTS
In this study, a chicken homologous Tie-2 protein vaccine (chTie-2) and a corresponding mouse Tie-2 vaccine as a control were prepared and the antitumor effect of these vaccines was tested in two tumor models (murine B16F10 melanoma and murine H22 hepatoma). Immunotherapy with chTie-2 was found effective in two tumor models. Autoantibodies against mouse Tie-2 were detected in sera of mice immunized with chTie-2 through Western blot analysis and ELISA assay. Anti-Tie-2 antibody-producing B cells were detectable by ELISPOT. Histologic examination revealed that autoantibodies were deposited on the endothelial cells of tumor tissues. Purified immunoglobulins from chTie-2-immunized mice could induce the apoptosis of human umbilical vein endothelial cells in vitro. Importantly, adoptive transfer of purified immunoglobulins led to antitumor effect in vivo; apparently, angiogenesis was significantly inhibited in these tumors. Furthermore, the antitumor activity and production of autoantibodies could be abrogated by depletion of CD4+ T lymphocytes.


CONCLUSIONS
Our findings may provide a vaccine strategy for cancer therapy and show the potential utilization of interference with Tie-2 pathway.
State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, People's Republic of China.
Yan
Y
Luo
Yan-Jun
YJ
Wen
Zhen-Yu
ZY
Ding
Chun-Hua
CH
Fu
Yang
Y
Wu
Ji-Yan
JY
Liu
Qiu
Q
Li
Qiu-Ming
QM
He
Xia
X
Zhao
Yu
Y
Jiang
Jiong
J
Li
Hong-Xin
HX
Deng
Bin
B
Kang
Yong-Qiu
YQ
Mao
Yu-Quan
YQ
Wei
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D045744:Cell Line, Tumor; D002645:Chickens; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D042787:Receptor, TIE-2 / Q000276:immunology*; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D022223:Vaccines, Subunit / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use
D019496:Cancer Vaccines; D007136:Immunoglobulins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D022223:Vaccines, Subunit; D042787:Receptor, TIE-2