肿瘤细胞治疗研究
英文原题：Dual targeting of BCMA and SLAMF7 with the CARtein system: chimeric antigen receptors with intein-mediated splicing elicit specific T cell activation against multiple myeloma.
Dual targeting of BCMA and SLAMF7 with the CARtein system: chimeric antigen receptors with intein-mediated splicing elicit specific T cell activation against multiple myeloma.
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这些结果表明，CARtein 平台是一种有前景、通用且高度特异的方法，可用于 CAR 的模块化设计与工程改造，在保持结构与功能完整性的同时实现多抗原靶向。
为解决传统 CAR-T 的局限，研究者开发了新型模块化 CAR 平台，同时靶向 BCMA 和 SLAMF7。该平台利用分裂内含肽介导的蛋白剪接机制，使 CAR 模块之间形成特异性共价肽键。此策略可保持近乎无缝的 CAR 结构，维持其整体完整性和功能。随后使用先进蛋白质结构预测软件进一步优化内含肽剪接 CAR 系统（称为 CARtein）的设计。
表达剪接 CARtein 构建体的细胞分别靶向 BCMA、SLAMF7 或同时靶向两种抗原，面对相应抗原时均显示强效且高度特异的活化。讨论：结果提示 CARtein 平台是模块化设计和工程化 CAR 的有前景、灵活且高度特异的方法，可实现多抗原靶向，同时维持结构和功能完整性。该模块化策略应对了传统 CAR-T 的关键局限，可能提高未来 MM 治疗的安全性和有效性。
To address the limitations of conventional CAR T therapy, we developed a novel modular CAR platform targeted against BCMA and SLAMF7. This was achieved using a split intein-mediated protein splicing mechanism, which allows specific covalent peptide bonds to form between CAR modules. This strategy maintains an almost seamless CAR structure, preserving its overall integrity and functionality. The design of the intein-spliced CAR system (termed "CARtein") was further optimized through advanced protein structure prediction software.
Cells expressing the spliced CARtein constructs, engineered to target BCMA, SLAMF7, or both antigens simultaneously, demonstrated robust and highly specific activation in response to their respective antigens. DISCUSSION: These results suggest that the CARtein platform is a promising, versatile, and highly specific approach for the modular design and engineering of CARs, enabling multi-antigen targeting while maintaining structural and functional integrity. This modular strategy addresses key limitations of conventional CAR T-cell therapy and may improve both the safety and effectiveness of future MM treatments.
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