Recombinant Immunotoxin Therapy of Glioblastoma: Smart Design, Key Findings, and Specific Challenges.
Recombinant Immunotoxin Therapy of Glioblastoma: Smart Design, Key Findings, and Specific Challenges.
复制标题
胶质母细胞瘤的重组免疫毒素疗法：智能设计、主要发现和具体挑战
DOI：
10.1155/2017/7929286
复制
发表时间：
2017
影响因子：
--
通讯作者：
Shan L
中科院分区：
文献类型：
--
作者：
Zhu S;Liu Y;Wang PC;Gu X;Shan L
重组免疫毒素（RIT）是指一组基于重组蛋白的治疗剂，其由两种组分组成：允许RIT特异性结合靶细胞的抗体可变片段或特异性配体和在内化后杀死靶细胞的工程化毒素片段。迄今为止，已经产生了1，000多个RIT，并且在血液恶性肿瘤的治疗中取得了重大成功。然而，RIT的免疫原性和脱靶毒性仍然是其应用于实体瘤治疗的重大障碍。还生成了一组用于治疗多形性胶质母细胞瘤的RIT，其中一些已在早期临床试验中证明了肿瘤缓解的证据以及可接受的毒性和安全性特征。与其他实体瘤不同的是，如何将RIT有效地输送到颅内肿瘤中是一个亟待解决的问题。本文首先回顾了RIT的设计和表达，然后总结了RIT治疗多形性胶质母细胞瘤的临床前和临床研究的关键发现，最后讨论了RIT治疗临床实践中仍然存在的具体问题。
Recombinant immunotoxins (RITs) refer to a group of recombinant protein-based therapeutics, which consists of two components: an antibody variable fragment or a specific ligand that allows RITs to bind specifically to target cells and an engineered toxin fragment that kills the target cells upon internalization. To date, over 1,000 RITs have been generated and significant success has been achieved in the therapy of hematological malignancies. However, the immunogenicity and off-target toxicities of RITs remain as significant barriers for their application to solid tumor therapy. A group of RITs have also been generated for the treatment of glioblastoma multiforme, and some have demonstrated evidence of tumor response and an acceptable profile of toxicity and safety in early clinical trials. Different from other solid tumors, how to efficiently deliver the RITs to intracranial tumors is more critical and needs to be solved urgently. In this article, we first review the design and expression of RITs, then summarize the key findings in the preclinical and clinical development of RIT therapy of glioblastoma multiforme, and lastly discuss the specific issues that still remain to forward RIT therapy to clinical practice.
登录
查看更多内容
影响因子：
2.8
作者：
Candolfi M;Kroeger KM;Xiong W;Liu C;Puntel M;Yagiz K;Muhammad AG;Mineharu Y;Foulad D;Wibowo M;Assi H;Baker GJ;Lowenstein PR;Castro MG
通讯作者：
Castro MG
影响因子：
4.2
作者：
Antignani A;Fitzgerald D
通讯作者：
Fitzgerald D
影响因子：
8.8
作者：
Schmidt, M;Vakalopoulou, E;Schneider, DW;Wels, W
通讯作者：
Wels, W
影响因子：
7.2
作者：
Chandramohan V;Bigner DD
通讯作者：
Bigner DD
影响因子：
6.4
作者：
Chandramohan, Vidyalakshmi;Bao, Xuhui;Kaneko, Mika Kato;Kato, Yukinari;Keir, Stephen T.;Szafranski, Scott E.;Kuan, Chien-Tsun;Pastan, Ira H.;Bigner, Darell D.
通讯作者：
Bigner, Darell D.