决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:CD7 CAR-T therapy: current developments, improvements, and dilemmas.
嵌合抗原受体(CAR)T细胞疗法是治疗复发或难治性(r/r)血液肿瘤的划时代免疫疗法,其在r/r B细胞来源恶性肿瘤中的成功应用已证明了这一点。
嵌合抗原受体(CAR)T细胞疗法是一种划时代的免疫疗法,用于治疗复发或难治性(r/r)血液肿瘤,其在r/r B细胞来源恶性肿瘤中的成功应用已证明了这一点。然而,在T细胞白血病或淋巴瘤中复制这一成功仍然具有挑战性。在各种潜在靶抗原中,CD7作为一个有前景的候选靶点已引起关注。CD7 CAR-T疗法是治疗r/r T细胞急性淋巴细胞白血病/淋巴母细胞淋巴瘤(T-ALL/LBL)和r/r急性髓系白血病(AML)研究最为广泛的方法之一。根据T细胞来源,CAR-T产品可分为自体产品和异体产品,两者均在临床试验中进行测试,各有其特定优势。异体CD7 CAR-T细胞在降低生产成本、确保质量一致性以及提高可负担性和可及性方面优于自体细胞。尽管具有这些优势,移植物抗宿主病(GVHD)、宿主抗移植物反应(HVGR)和自相残杀等挑战对异体CD7 CAR-T细胞的临床应用构成了重大障碍。然而,创新的基因编辑技术,如CRISPR/Cas9和碱基编辑,以及更有前景的细胞来源,如自然杀伤T(NKT)细胞和诱导多能干细胞(iPSCs),正在成为潜在的解决方案。在这篇综述中,我们讨论了CD7 CAR-T产品的不同类别、其在临床环境中的应用以及改进方向。
Chimeric antigen receptor (CAR) T-cell therapy is an epoch-making immunotherapy for the treatment of relapsed or refractory (r/r) blood tumors, as demonstrated by its successful implementation in r/r B cell-derived malignancies. However, replicating this success in T-cell leukemia or lymphoma remains challenging. Among the various potential target antigens, CD7 has garnered attention as a promising candidate. CD7 CAR-T therapy is one of the most extensively studied approaches for treating r/r T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) and r/r acute myeloid leukemia (AML). Based on the source of T cells, CAR-T products can be categorized as autologous and allogeneic, both of which are being tested in clinical trials, each offering specific advantages. Allogeneic CD7 CAR-T cells outperform autologous cells in terms of reducing manufacturing costs, ensuring consistent quality, and improving affordability and availability. Despite these advantages, challenges like graft-versus-host disease (GVHD), host-versus-graft reaction (HVGR), and fratricide pose significant barriers to the clinical application of allogeneic CD7 CAR-T cells. However, innovative gene-editing techniques, such as CRISPR/Cas9 and base editing, and more promising cell sources, such as natural killer T (NKT) cells and induced pluripotent stem cells (iPSCs), are emerging as potential solutions. In this review, we discuss the different categories of CD7 CAR-T products, their application in clinical settings, and directions for refinement.
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