This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Luo, Y. Articles by Wei, Y.-Q. Search for Related Content PubMed PubMed Citation Articles by Luo, Y. Articles by Wei, Y.-Q.

Immunotherapy of Tumors with Protein Vaccine Based on Chicken Homologous Tie-2

Authors' Affiliation: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, People's Republic of China

Requests for reprints: Yu-Quan Wei, State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, People's Republic of China. E-mail: yuquawei{at}vip.sina.com.

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.