肿瘤细胞治疗研究
英文原题：RevCAR-expressing immune effector cells for targeting of Fn14-positive glioblastoma.
在最近的研究中，我们建立了独特的衔接器嵌合抗原受体（CAR）平台RevCAR，该平台使用肽表位作为细胞外CAR结构域，而不是抗体结构域。
在最近的研究中，我们建立了一种独特的适配体嵌合抗原受体（CAR）平台RevCAR，其使用肽表位作为细胞外CAR结构域，而不是抗体结构域。RevCAR适配体（称为RevCAR靶向模块，RevTM）是双特异性抗体，能够实现RevCAR系统的可逆ON/OFF开关，与常规CAR相比提高了安全性。在此，我们首次描述了其用于重定向T细胞和NK-92细胞的应用。此外，我们描述了一种新型RevTM的开发和临床前验证，该RevTM靶向成纤维细胞生长因子诱导型14（Fn14）表面受体，该受体在胶质母细胞瘤（GBM）细胞上过表达，因此可作为治疗GBM的有前景靶点。这种新型RevTM有效重定向RevCAR修饰的T细胞和NK-92细胞，并在体外和体内导致GBM细胞杀伤。肿瘤细胞杀伤与IL-2、TNF-α和/或IFN-γ分泌增加相关。因此，这些发现揭示了RevCAR T和NK-92系统作为针对GBM的安全且特异性免疫治疗方法的互补潜力。
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.
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