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抗独特型单链模拟 CA125 与 tuftsin 相连,为小鼠提供了针对卵巢癌的保护性免疫。

Anti-idiotypic single chain mimicking CA125 linked with tuftsin provides protective immunity against ovarian cancer in mice.

机构信息

State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, PR China.

出版信息

Mol Med Rep. 2012 Feb;5(2):388-94. doi: 10.3892/mmr.2011.643. Epub 2011 Oct 21.

Abstract

The activation of effector cells by bifunctional proteins to kill target cells has great potential in the treatment of cancer. In this study, a recombinant fusion protein composed of an anti‑idiotypic single chain mimicking CA125 connected with tuftsin by an artificial linker was constructed. The fusion protein was found to manifest a number of biological activities, including activation of macrophages and stimulation of the T-cell response against cancer. Compared with single‑chain Fv without tuftsin, the fusion protein showed stronger immunogenicity triggering humoral and cellular immune responses in mice. Fusion of tuftsin to scFv resulted in enhanced production of anti-anti-idiotypic antibodies and T-cell response. Protection against tumor challenges may be achieved in animals immunized with fusion protein. These results raise the possibility of employing cancer immunotherapy by administration of fusion proteins composed of anti‑idiotypic antibodies and tuftsin.

摘要

双功能蛋白激活效应细胞杀伤靶细胞在癌症治疗中有很大的潜力。在这项研究中,构建了一种由抗独特型单链通过人工连接子与 tuftsin 连接而成的重组融合蛋白。该融合蛋白表现出多种生物学活性,包括激活巨噬细胞和刺激针对癌症的 T 细胞反应。与没有 tuftsin 的单链 Fv 相比,融合蛋白表现出更强的免疫原性,在小鼠中引发体液和细胞免疫反应。tuftsin 与 scFv 的融合导致抗抗独特型抗体和 T 细胞反应的产生增强。用融合蛋白免疫的动物可能会获得对肿瘤挑战的保护。这些结果提出了通过给予由抗独特型抗体和 tuftsin 组成的融合蛋白来进行癌症免疫治疗的可能性。

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