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:HSCT and CAR-T: a power couple-but who serves whom?
造血干细胞移植(HSCT)和CAR-T 细胞疗法是血液系统恶性肿瘤的两种主要治疗手段。
造血干细胞移植(HSCT)和CAR-T 细胞治疗是血液系统恶性肿瘤的两种主要治疗手段。HSCT 可通过预处理诱导的肿瘤细胞减灭、免疫重建和移植物抗白血病效应提供持久的疾病控制,而 CAR-T 治疗提供抗原特异性抗肿瘤活性,并重塑了复发或难治性白血病、淋巴瘤和多发性骨髓瘤(MM)的治疗格局。尽管有这些进展,这两种治疗手段仍面临多重挑战。HSCT 受限于疾病复发和移植相关并发症,而 CAR-T 治疗则受到抗原逃逸、持续性有限和治疗相关毒性的挑战。越来越多的临床经验表明,不应将 HSCT 和 CAR-T 治疗视为相互竞争的策略,而应视为互补的治疗方法,其价值取决于疾病特征、缓解深度、免疫恢复和移植可行性。一方面,CAR-T 治疗可在移植前降低肿瘤负荷、纳入改良预处理方案,或在异基因 HSCT(allo-HSCT)后作为预防性、抢先性或挽救性细胞治疗使用。另一方面,HSCT 可巩固 CAR-T 诱导的缓解,在特定情况下提供造血支持,并创造可能促进后续 CAR-T 细胞治疗的移植后免疫环境。在本综述中,我们总结了 HSCT-CAR-T 整合在白血病、淋巴瘤和 MM 中的当前证据。我们讨论主要的整合策略,包括 CAR-T 治疗后的 HSCT、CAR-T 辅助预处理、自体干细胞移植(ASCT)-CAR-T 序贯策略,以及 allo-HSCT 后的 CAR-T 治疗。我们旨在帮助将合适的患者匹配到最合适的 HSCT-CAR-T 策略,从而改善临床决策。
Hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor T-cell (CAR-T) therapy are two major therapeutic approaches for hematologic malignancies. HSCT can provide durable disease control through conditioning-induced tumor cytoreduction, immune reconstitution, and graft-versus-leukemia effects, whereas CAR-T therapy provides antigen-specific antitumor activity and has reshaped the treatment landscape for relapsed or refractory leukemia, lymphoma, and multiple myeloma (MM). Despite these advances, both therapeutic approaches continue to face multiple challenges. HSCT is limited by disease relapse and transplant-related complications, while CAR-T therapy is challenged by antigen escape, limited persistence, and treatment-related toxicities. Increasing clinical experience suggests that HSCT and CAR-T therapy should not be viewed as competing strategies, but rather as complementary therapeutic approaches whose value depends on disease characteristics, depth of response, immune recovery, and transplant feasibility. On the one hand, CAR-T therapy can reduce tumor burden before transplantation, be incorporated into modified conditioning regimens, or be used after allogeneic HSCT (allo-HSCT) as prophylactic, preemptive, or salvage cellular therapy. On the other hand, HSCT can consolidate CAR-T-induced remission, provide hematopoietic support in selected settings, and create a post-transplant immune environment that may facilitate subsequent CAR-T-cell therapy. In this review, we summarize the current evidence for HSCT-CAR-T integration in leukemia, lymphoma, and MM. We discuss major integration strategies, including HSCT after CAR-T therapy, CAR-T-assisted conditioning, autologous stem cell transplantation (ASCT)-CAR-T sequential strategies, and CAR-T therapy after allo-HSCT. We aim to help match appropriate patients to the most suitable HSCT-CAR-T strategies and thereby improve clinical decision-making.
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