Immunotherapy of tumors with protein vaccine based on chicken homologous Tie-2
Immunotherapy of tumors with protein vaccine based on chicken homologous Tie-2
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DOI：
10.1158/1078-0432.ccr-05-1990
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发表时间：
2006-03-15
影响因子：
11.5
通讯作者：
Wei, YQ
中科院分区：
文献类型：
--
作者：
Luo, Y;Wen, YJ;Wei, YQ
目的：Tie-2是一种内皮特异性受体酪氨酸激酶，在肿瘤血管生成中起关键作用。本研究以鸡Tie-2蛋白为模型抗原，通过异种同源Tie-2与自身Tie-2的交叉反应，打破对Tie-2的免疫耐受，探索肿瘤免疫治疗的可行性。在本研究中，鸡同源Tie-2蛋白疫苗（chTie-2）和相应的小鼠Tie-2蛋白疫苗，2疫苗作为对照，并在两种肿瘤模型（鼠B16 F10黑色素瘤和鼠H22肝癌）中测试这些疫苗的抗肿瘤效果。发现用chTie-2的免疫疗法在两种肿瘤模型中有效。用chTie-2免疫小鼠，通过Western blot和ELISA检测血清中抗小鼠Tie-2的自身抗体。通过ELISPOT可检测到产生抗Tie-2抗体的B细胞。组织学检查显示，自身抗体沉积在肿瘤组织的内皮细胞上。chTie-2免疫小鼠的纯化免疫球蛋白在体外可诱导人脐静脉内皮细胞凋亡。重要的是，过继转移纯化的免疫球蛋白导致体内抗肿瘤作用;显然，血管生成在这些肿瘤中被显著抑制。结论：我们的研究结果可能为肿瘤治疗提供一种疫苗策略，并显示了干扰Tie-2通路的潜在用途。
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.