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:SOHO State of the Art Updates and Next Questions | CD7 CAR-T Therapy for Treating CD7-Positive Hematological Malignancies: Clinical Advances and Future Directions.
CD7 CAR-T细胞疗法已成为治疗复发/难治性(R/R)CD7阳性血液系统恶性肿瘤的一种有前景的疗法,为治疗选择有限的患者带来了新的希望。
CD7 CAR-T细胞疗法已成为治疗复发/难治性(R/R)CD7阳性血液系统恶性肿瘤的一种有前景方法,为治疗选择有限的患者带来新希望。本综述考察CD7 CAR-T疗法近期临床进展、挑战和未来方向。临床试验显示,CD7CAR-T(CD7 CAR-T)细胞治疗T细胞急性淋巴细胞白血病(T-ALL)、T细胞淋巴母细胞淋巴瘤(T-LBL)及其他CD7阳性恶性肿瘤疗效显著,骨髓完全缓解(CR)率达90%–95%,髓外病变(EMD)完全缓解率为50%–60%。为克服自相残杀等挑战,研究者开发了多种工程策略,包括自然筛选的CD7靶向CAR-T细胞、基因编辑、蛋白阻断剂及通用型CAR-T细胞。尽管CD7 CAR-T疗法初始应答良好,持久缓解通常依赖巩固性异基因造血干细胞移植(allo-HSCT)。目前研究重点是优化CAR设计、改善CAR-T细胞持久性,并开发新型联合策略以改善长期结局。整体安全性可控,主要关注细胞因子释放综合征(CRS)和神经毒性。然而,长期血细胞减少,以及清除健康CD7阳性细胞后可能造成的长期免疫缺陷,仍是积极研究的领域。随着CD7 CAR-T疗法不断发展,未来方向包括完善患者选择、探索双靶向策略,以及研究CAR-T与allo-HSCT的创新整合方式。这些进展旨在提升CD7阳性血液系统恶性肿瘤患者接受CD7 CAR-T治疗的疗效、安全性和可及性。
CD7 CAR-T cell therapy has emerged as a promising treatment for relapsed/refractory (R/R) CD7-positive hematological malignancies, offering new hope for patients with limited therapeutic options. This review examines the recent clinical advances, challenges, and future directions of CD7 CAR-T therapy. Clinical trials have demonstrated remarkable efficacy of CD7 chimeric antigen receptor T (CD7 CAR-T) cells in treating T-cell acute lymphoblastic leukemia (T-ALL), T-cell lymphoblastic lymphoma (T-LBL), and other CD7-positive malignancies, with complete remission (CR) rates of 90-95% in bone marrow (BM) and 50% to 60% in extramedullary disease (EMD). Various engineering strategies, including naturally selected CD7-targeted CAR-T cells, gene editing, protein blockers and universal CAR-T cells, have been developed to overcome challenges such as fratricide. While CD7 CAR-T therapy has shown promising initial responses, durable remissions often depend on consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ongoing research is focused on optimizing CAR designs, improving CAR-T cell persistence, and developing novel combination strategies to enhance long-term outcomes. Safety profiles have been generally manageable, with cytokine release syndrome (CRS) and neurotoxicity being the primary concerns. However, prolonged cytopenias and potential long-term immunodeficiency due to depletion of healthy CD7-positive cells remain areas of active investigation. As CD7 CAR-T therapy continues to evolve, future directions include refining patient selection, exploring dual-targeting approaches, and investigating innovative strategies to integrate CAR-T therapy with allo-HSCT. These advancements aim to improve the efficacy, safety, and accessibility of CD7 CAR-T therapy for patients with CD7-positive hematological malignancies.
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