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Active immunotherapy of tumors with a recombinant xenogeneic endoglin as a model antigen
Authors:Tan Guang-Hong  Wei Yu-Quan  Tian Ling  Zhao Xia  Yang Li  Li Jiong  He Qiu-Ming  Wu Yang  Wen Yan-Jun  Yi Tao  Ding Zhen-Yu  Kan Bin  Mao Yong-Qiu  Deng Hong-Xin  Li Hong-Li  Zhou Chun-Hua  Fu Chun-Hua  Xiao Fei  Zhang Xiao-Wei
Affiliation:Key Laboratory of Biotherapy of Human Diseases, Ministry of Education, P R China.
Abstract:Angiogenesis play a critical role in tumor growth and metastasis. Increasing evidence suggests that endoglin is a powerful marker of angiogenesis in solid malignancies. Thus, breaking of immune tolerance of self-endoglin-associated angiogenesis is an attractive approach to cancer therapy. To test this concept, we recombined the extracellular domains of porcine endoglin, and used it as a xenogeneic vaccine. We found that immunotherapy with porcine endoglin was effective at both protective and therapeutic anti-tumor immunity in several mouse tumor models. Autoantibodies against mouse endoglin were identified by Western blot and ELISA. IgG1 and IgG2b were substantially increased. Anti-endoglin antibody-producing B cells were detectable by ELISPOT assay. There was endothelial deposition of immunoglobulins within tumors. The anti-tumor activity was also induced by the adoptive transfer of the purified immunoglobulins. Angiogenesis was apparently inhibited within the tumor tissues and on the alginate beads. The increased apoptotic cells were found within the tumor tissues from the mice treated with porcine endoglin. The anti-tumor activity and production of autoantibodies against mouse endoglin could be abrogated by depletion of CD4(+) T lymphocytes. Remarkably, no marked toxicity was found in the immunized mice. These observations may provide an alternative rational strategy for active cancer immunotherapy.
Keywords:Tumor angiogenesis  Active immunotherapy  Endoglin  Recombinant protein  Vaccine
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