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用于癌症治疗的临床靶向重组免疫毒素

Clinical targeting recombinant immunotoxins for cancer therapy.

作者信息

Li Meng, Liu Zeng-Shan, Liu Xi-Lin, Hui Qi, Lu Shi-Ying, Qu Lin-Lin, Li Yan-Song, Zhou Yu, Ren Hong-Lin, Hu Pan

机构信息

Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, China-Japan Union Hospital, The First Hospital, Jilin University, Changchun.

School of Pharmacy, Wenzhou Medical University, Wenzhou, People's Republic of China.

出版信息

Onco Targets Ther. 2017 Jul 20;10:3645-3665. doi: 10.2147/OTT.S134584. eCollection 2017.

Abstract

Recombinant immunotoxins (RITs) are proteins that contain a toxin fused to an antibody or small molecules and are constructed by the genetic engineering technique. RITs can bind to and be internalized by cells and kill cancerous or non-cancerous cells by inhibiting protein synthesis. A wide variety of RITs have been tested against different cancers in cell culture, xenograft models, and human patients during the past several decades. RITs have shown activity in therapy of several kinds of cancers, but different levels of side effects, mainly related to vascular leak syndrome, were also observed in the treated patients. High immunogenicity of RITs limited their long-term or repeat applications in clinical cases. Recent advances in the design of immunotoxins, such as humanization of antibody fragment, PEGylation, and modification of human B- and T-cell epitopes, are overcoming the above mentioned problems, which predict the use of these immunotoxins as a potential therapeutic method to treat cancer patients.

摘要

重组免疫毒素(RITs)是一类蛋白质,其包含与抗体或小分子融合的毒素,通过基因工程技术构建而成。RITs能够与细胞结合并被细胞内化,通过抑制蛋白质合成来杀死癌细胞或非癌细胞。在过去几十年中,多种RITs已在细胞培养、异种移植模型和人类患者中针对不同癌症进行了测试。RITs在几种癌症的治疗中显示出活性,但在接受治疗的患者中也观察到了不同程度的副作用,主要与血管渗漏综合征有关。RITs的高免疫原性限制了它们在临床病例中的长期或重复应用。免疫毒素设计方面的最新进展,如抗体片段人源化、聚乙二醇化以及人B细胞和T细胞表位修饰,正在克服上述问题,这预示着这些免疫毒素有望作为一种治疗癌症患者的潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8d1/5530862/ffa110c2023a/ott-10-3645Fig1.jpg

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