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:Chimeric Antigen Receptor T Cell Therapy versus Hematopoietic Stem Cell Transplantation: An Evolving Perspective.
细胞治疗手段,包括自体(auto-)造血细胞移植(HCT)、异基因(allo-)HCT 以及如今的嵌合抗原受体(CAR)T 细胞治疗,已在晚期血液系统恶性肿瘤中展现出长期缓解。
自体造血细胞移植(auto-HCT)、异基因造血细胞移植(allo-HCT)及新兴的嵌合抗原受体(CAR)T细胞疗法等细胞治疗方式,已在晚期血液系统恶性肿瘤中实现长期缓解。auto-HCT和allo-HCT通过造血重建,使患者能够接受更高剂量化疗。allo-HCT还引入非特异性免疫介导的肿瘤靶向作用,降低复发风险,但也会同样攻击宿主正常细胞。相比之下,CAR-T疗法通过基因工程化的精准免疫治疗,以抗原特异性且不依赖MHC的方式将自体免疫效应细胞重新导向恶性肿瘤,在对细胞毒性化疗耐药的患者中已显示疗效。不过,CAR-T也有其独特毒性和挑战。目前已有成熟CAR-T产品并广泛应用的主要疾病包括非霍奇金淋巴瘤(大B细胞、套细胞及滤泡性淋巴瘤)、B细胞急性淋巴细胞白血病和多发性骨髓瘤。近期及正在进行的临床试验研究三种细胞治疗方式(auto-HCT、allo-HCT和CAR-T)之间的关系,以确定它们应作为“互补”还是“竞争”疗法。本综述结合最新数据审视这一关系,并讨论可能影响临床决策的争议和结论。
Cellular therapy modalities, including autologous (auto-) hematopoietic cell transplantation (HCT), allogeneic (allo-) HCT, and now chimeric antigen receptor (CAR) T cell therapy, have demonstrated long-term remission in advanced hematologic malignancies. Auto-HCT and allo-HCT, through hematopoietic rescue, have permitted the use of higher doses of chemotherapy. Allo-HCT also introduced a nonspecific immune-mediated targeting of malignancy resulting in protection from relapse, although at the expense of similar targeting of normal host cells. In contrast, CAR T therapy, through genetically engineered immunotherapeutic precision, allows for redirection of autologous immune effector cells against malignancy in an antigen-specific and MHC-independent fashion, with demonstrated efficacy in patients who are refractory to cytotoxic chemotherapy. It too has unique toxicities and challenges, however. Non-Hodgkin lymphoma (including large B cell lymphoma, mantle cell lymphoma, and follicular lymphoma), B cell acute lymphoblastic leukemia, and multiple myeloma are the 3 main diseases associated with the use of fully developed CAR T products with widespread deployment. Recent and ongoing clinical trials have been examining the interface among the 3 cellular therapy modalities (auto-HCT, allo-HCT, and CAR T) to determine whether they should be "complementary" or "competitive" therapies. In this review, we examine the current state of this interface with respect to the most recent data and delve into the controversies and conclusions that may inform clinical decision making.
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