文章：

表达RevCAR的免疫效应细胞用于靶向Fn14阳性胶质母细胞瘤

RevCAR-expressing immune effector cells for targeting of Fn14-positive glioblastoma 

原文发布日期：2024-04-06

英文摘要：

In recent studies, we have established the unique adapter chimeric antigen receptor (CAR) platform RevCAR which uses, as an extracellular CAR domain, a peptide epitope instead of an antibody domain. RevCAR adapters (termed RevCAR target modules, RevTMs) are bispecific antibodies that enable the reversible ON/OFF switch of the RevCAR system, improving the safety compared to conventional CARs. Here, we describe for the first time its use for retargeting of both T and NK-92 cells. In addition, we describe the development and preclinical validation of a novel RevTM for targeting of the fibroblast growth factor-inducible 14 (Fn14) surface receptor which is overexpressed on Glioblastoma (GBM) cells, and therefore serves as a promising target for the treatment of GBM. The novel RevTM efficiently redirects RevCAR modified T and NK-92 cells and leads to the killing of GBM cells both in vitro and in vivo. Tumor cell killing is associated with increased IL-2, TNF-α and/or IFN-γ secretion. Hence, these findings give an insight into the complementary potential of both RevCAR T and NK-92 systems as a safe and specific immunotherapeutic approach against GBM. 

摘要翻译：

在近期研究中，我们成功构建了独特的适配体嵌合抗原受体（CAR）平台——RevCAR。该平台使用肽表位而非抗体结构域作为胞外CAR区域，其适配体（称为RevCAR靶向模块，RevTM）是一种双特异性抗体，可实现RevCAR系统的可逆性开关控制，较传统CAR系统具有更高的安全性。本文首次报道了该平台在T细胞和NK-92细胞双重靶向中的应用。此外，我们开发并完成了针对成纤维细胞生长因子诱导型14（Fn14）表面受体的新型RevTM临床前验证——该受体在胶质母细胞瘤（GBM）细胞中过度表达，因此成为治疗GBM的潜力靶点。新型RevTM能有效引导经RevCAR修饰的T细胞和NK-92细胞，在体外和体内实验中均实现对GBM细胞的杀伤作用。该杀伤效应与白细胞介素-2（IL-2）、肿瘤坏死因子-α（TNF-α）和/或γ干扰素（IFN-γ）分泌增加相关。这些发现揭示了RevCAR-T细胞与RevCAR-NK-92系统作为安全精准的GBM免疫治疗手段具有互补潜力。

原文链接：

RevCAR-expressing immune effector cells for targeting of Fn14-positive glioblastoma