肿瘤细胞治疗研究
英文原题：Dual-targeting CAR T cells for B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma.
Dual-targeting CAR T cells for B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma.
涵盖所有生产策略的 1 期和 2 期试验显示，这是一种安全的方法，具有相当的缓解率和初始产品扩增。
CD19靶向嵌合抗原受体（CAR）T细胞疗法后复发，仍是B细胞急性淋巴细胞白血病（ALL）及B细胞非霍奇金淋巴瘤（B-NHL）的重大挑战。为避免CD19阴性复发，主要策略之一是开发同时靶向CD19和另一靶点（如CD22或CD20）的双靶CAR-T细胞。实现方法包括共同给予两种各自靶向单一抗原的产品、共同转导自体T细胞、使用双顺反子载体，或开发双价CAR。在所有制备策略的I期和II期试验中，这些方法均显示安全，缓解率和初始产品扩增情况相当。CAR-T细胞持久性仍是重大问题，输注CAR-T后多数复发为抗原阳性。此外，尽管增加了第二种靶抗原，抗原阴性复发仍未被消除。本综述总结双靶CAR-T细胞治疗B-ALL和B-NHL的最新进展、面临的挑战及可能的后续改进方向。
Relapse after CD19-directed chimeric antigen receptor (CAR) T-cell therapy remains a major challenge in B-cell acute lymphoblastic leukemia (ALL) and B-cell non-Hodgkin lymphoma (B-NHL). One of the main strategies to avoid CD19-negative relapse has been the development of dual CAR T cells targeting CD19 and an additional target, such as CD22 or CD20. Different methods have been used to achieve this, including coadministration of 2 products targeting 1 single antigen, cotransduction of autologous T cells, use of a bicistronic vector, or the development of bivalent CARs. Phase 1 and 2 trials across all manufacturing strategies have shown this to be a safe approach with equivalent remission rates and initial product expansion. CAR T-cell persistence remains a significant issue, with the majority of relapses being antigen-positive after CAR T-cell infusion. Further, despite adding a second antigen, antigen-negative relapses have not yet been eliminated. This review summarizes the state of the art with dual-targeting CAR T cells for B-cell ALL and B-NHL, the challenges encountered, and possible next steps to overcome them.
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