Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße 400, D-01328 Dresden, Germany.
Mildred Scheel Early Career Center, Faculty of Medicine Carl Gustav Carus, TU Dresden, D-01307 Dresden, Germany.
Int J Mol Sci. 2022 Apr 28;23(9):4920. doi: 10.3390/ijms23094920.
Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases. Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system. The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells. Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies.
嵌合抗原受体 (CAR)-表达 T 细胞无疑是血液系统恶性肿瘤的突破性治疗方法。尽管取得了成功,但临床经验揭示了一些挑战,包括在 B 细胞急性淋巴细胞白血病 (B-ALL) 中针对单一抗原(如 CD19)靶向治疗后复发,以及在某些情况下可能出现严重的副作用。因此,显然需要考虑改进安全性方法和靶向多个抗原,以进一步改善 CAR T 细胞治疗 B-ALL。在本文中,我们通过研究使用 CD10 作为我们的开关型 UniCAR 系统治疗 B-ALL 的治疗靶点来解决这两个问题。UniCAR 平台是一个模块化平台,依赖于两个元素的存在才能发挥作用。这些包括 UniCAR T 细胞和靶模块 (TM),它们将 T 细胞与肿瘤细胞上的各自靶标交联。TM 作为控制 UniCAR T 细胞开关性的关键。在这里,我们证明了武装有抗 CD10 TM 的 UniCAR T 细胞可以有效地杀死 B-ALL 细胞系以及患者来源的 B-ALL 母细胞,从而突出了将 CD10 用作 B 细胞恶性肿瘤新兴治疗靶点的令人兴奋的可能性。