肿瘤细胞治疗研究
英文原题：Meditope-Enabled Chimeric Antigen Receptors Facilitate Plug-and-Play Control of T Cells.
Meditope-Enabled Chimeric Antigen Receptors Facilitate Plug-and-Play Control of T Cells.
嵌合抗原受体（CAR）T细胞已经改变了癌症治疗，但实现更广泛的临床成功仍面临挑战，包括克服肿瘤抗原异质性和有限的T细胞适应性。
嵌合抗原受体（CAR）T细胞已经改变了癌症治疗，但实现更广泛的临床成功仍面临挑战，包括克服肿瘤抗原异质性和有限的T细胞适应性。为应对这些挑战并增强CAR T细胞功能，我们利用了meditope技术，这是一种锁钥平台，其中抗体的Fab区域被修饰以结合一种称为meditope（meP）的小环状肽。我们开发了一组基于meditope-enabled Fab的CAR（meCAR），其显示出对meP的选择性结合，并与传统的基于单链可变片段（scFv）的CAR具有相当的活性。聚焦于靶向HER2的meCAR以评估平台实用性，我们利用meditope平台的模块化特性，使用meP融合荧光剂检测meCAR T细胞，通过meP融合IL-15细胞因子促进meCAR T细胞扩增，并通过meP融合抗体拓宽肿瘤抗原靶向以应对肿瘤异质性。这些发现确立了meditope技术作为一种多功能策略，以增强CAR T细胞功能并克服当前基于CAR的疗法的关键局限性。
Chimeric antigen receptor (CAR) T cells have transformed cancer treatment, yet challenges for achieving broader clinical success remain, including overcoming tumor antigen heterogeneity and limited T-cell fitness. To address these challenges and enhance CAR T-cell functionality, we leveraged meditope technology, a lock-and-key platform where Fab regions of antibodies are modified to bind a small cyclic peptide termed meditope (meP). We developed a panel of meditope-enabled Fab-based CARs (meCARs), which showed selective binding to the meP and comparable activity to traditional single-chain variable fragment (scFv)-based CARs. Focusing on HER2-targeted meCARs for evaluating platform utility, we exploited the modularity of the meditope platform to detect meCAR T cells using meP-fused fluorescent agents, promote meCAR T-cell expansion via meP-fused IL-15 cytokine, and broaden tumor antigen targeting through meP-fused antibodies to address tumor heterogeneity. These findings establish the meditope technology as a versatile strategy to augment CAR T-cell functionality and overcome key limitations of current CAR-based therapies.
MEMBER ACCOUNT
登录成功会直接打开下一页。
