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CD176 抗血清治疗可导致白血病小鼠模型的治疗反应。

CD176 antiserum treatment leads to a therapeutic response in a murine model of leukemia.

机构信息

Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, P.R. China.

出版信息

Oncol Rep. 2013 Oct;30(4):1841-7. doi: 10.3892/or.2013.2639. Epub 2013 Jul 25.

Abstract

CD176 (Thomsen-Friedenreich antigen) is a tumor-associated carbohydrate structure. CD176 is expressed at the surface of human leukemic cells but is almost absent in normal and benign adult human tissues. Therefore, CD176 could be a promising target for antitumor immunotherapy. In the present study, pre-immunization with asialoglycophorin A (containing the CD176 oligosaccharide chains) was able to significantly improve the survival time of mice carrying CD176+ leukemia as compared to the control mice without the immunization. Furthermore, the passive transfer of CD176 antiserum which reacted only with the tumor-associated CD176 in cancer cells, was able to effectively prolong the survival time of CD176+ leukemia mice. In particular, the CD176 antiserum treatment could inhibit the growth and spreading of CD176+ leukemic cells in bone marrow, spleen, liver, and lung as evidenced by histopathological examination. CD176 antiserum could induce the apoptosis of CD176+ leukemic cells in vivo in a manner as previously observed in vitro. The data provided strong evidence that both CD176 antigen-based active immunotherapy and CD176 antibody-based passive immunotherapy lead to a therapeutic response in CD176+ leukemia mice. Therefore, both CD176 vaccine and CD176 antibody drug may be beneficial for the treatment of CD176+ leukemia patients.

摘要

CD176(Thomson-Friedenreich 抗原)是一种肿瘤相关的碳水化合物结构。CD176 表达于人类白血病细胞表面,但在正常和良性成人组织中几乎不存在。因此,CD176 可能是抗肿瘤免疫治疗的一个有前途的靶点。在本研究中,与未免疫的对照组小鼠相比,预先用含 CD176 寡糖链的去唾液酸糖蛋白 A 进行免疫接种,能够显著延长携带 CD176+白血病的小鼠的生存时间。此外,仅与癌细胞中肿瘤相关的 CD176 反应的 CD176 抗血清的被动转移,能够有效地延长 CD176+白血病小鼠的生存时间。特别是,组织病理学检查证实,CD176 抗血清治疗能够抑制骨髓、脾脏、肝脏和肺部 CD176+白血病细胞的生长和扩散。CD176 抗血清能够在体内以体外观察到的方式诱导 CD176+白血病细胞的凋亡。这些数据提供了强有力的证据,表明基于 CD176 抗原的主动免疫治疗和基于 CD176 抗体的被动免疫治疗都能使 CD176+白血病小鼠产生治疗反应。因此,CD176 疫苗和 CD176 抗体药物都可能有益于治疗 CD176+白血病患者。

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