Retargeted human avidin-CAR T cells for adoptive immunotherapy of EGFRvIII expressing gliomas and their evaluation via optical imaging.
Retargeted human avidin-CAR T cells for adoptive immunotherapy of EGFRvIII expressing gliomas and their evaluation via optical imaging.
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重新靶向人类亲和素-CAR T 细胞用于表达 EGFRvIII 的神经胶质瘤的过继免疫治疗及其通过光学成像的评估。
DOI：
10.18632/oncotarget.4362
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发表时间：
2015-09-15
期刊：
影响因子：
--
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Liu K;Liu X;Peng Z;Sun H;Zhang M;Zhang J;Liu S;Hao L;Lu G;Zheng K;Gong X;Wu D;Wang F;Shen L
嵌合抗原受体（CAR）的设计已经取得了重大进展，过继免疫治疗靶向肿瘤相关抗原。然而，在真实的时间内监测治疗的挑战一直被忽视。为了解决这个问题，我们开发了光学分子成像方法来评估最近报道的针对表达EGFRvIII的胶质瘤异种移植物的过继免疫治疗的新型CAR策略。我们最初生物素化一种新的抗EGFRvIII单克隆抗体（生物素-4G1）以预靶向EGFRvIII+神经胶质瘤，然后针对预靶向的生物素-4G1重定向活化的抗生物素蛋白-CAR表达T细胞。通过光学成像研究和生物分布分析，我们确定了前靶点和靶点的特异性，并确定了体内T细胞过继转移的最佳时间。结果表明，这种治疗策略对携带EGFRvIII+胶质瘤的小鼠提供了有效的治疗效果，并暗示光学成像是未来辅助指导临床CAR-T细胞过继转移的非常有用的工具。
There has been significant progress in the design of chimeric antigen receptors (CAR) for adoptive immunotherapy targeting tumor-associated antigens. However, the challenge of monitoring the therapy in real time has been continually ignored. To address this issue, we developed optical molecular imaging approaches to evaluate a recently reported novel CAR strategy for adoptive immunotherapy against glioma xenografts expressing EGFRvIII. We initially biotinylated a novel anti-EGFRvIII monoclonal antibody (biotin-4G1) to pre-target EGFRvIII+ gliomas and then redirect activated avidin-CAR expressing T cells against the pre-targeted biotin-4G1. By optical imaging study and bio-distribution analysis, we confirmed the specificity of pre-target and target and determined the optimal time for T cells adoptive transfer in vivo. The results showed this therapeutic strategy offered efficient therapy effect to EGFRvIII+ glioma-bearing mice and implied that optical imaging is a highly useful tool in aiding in the instruction of clinical CAR-T cells adoptive transfer in future.