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Immunotherapy of tumors with protein vaccine based on chicken homologous Tie-2.
Luo, Yan; Wen, Yan-Jun; Ding, Zhen-Yu; Fu, Chun-Hua; Wu, Yang; Liu, Ji-Yan; Li, Qiu; He, Qiu-Ming; Zhao, Xia; Jiang, Yu; Li, Jiong; Deng, Hong-Xin; Kang, Bin; Mao, Yong-Qiu; Wei, Yu-Quan.
Afiliación
  • Luo Y; State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, People's Republic of China.
Clin Cancer Res ; 12(6): 1813-9, 2006 Mar 15.
Article en En | MEDLINE | ID: mdl-16551866
PURPOSE: 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. EXPERIMENTAL DESIGN AND 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.
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Bases de datos: MEDLINE Asunto principal: Vacunas contra el Cáncer / Receptor TIE-2 / Inmunoterapia / Neoplasias Experimentales Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2006 Tipo del documento: Article
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Bases de datos: MEDLINE Asunto principal: Vacunas contra el Cáncer / Receptor TIE-2 / Inmunoterapia / Neoplasias Experimentales Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2006 Tipo del documento: Article