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:CAR T-cells for acute leukemias in children: current status, challenges, and future directions.
CAR T-cells for acute leukemias in children: current status, challenges, and future directions.
CAR-T 细胞疗法被视为白血病最有前景的免疫疗法之一,因为靶向 CD19 已彻底改变了儿童、青少年和年轻成人复发/难治性 B 细胞急性淋巴细胞白血病(B-ALL)的治疗。
CAR-T细胞疗法被视为白血病最有前景的免疫疗法之一,因为靶向CD19已改变儿童、青少年及年轻成人复发/难治性B细胞急性淋巴细胞白血病(B-ALL)的治疗。早期临床试验显示初始应答率很高,且后续随访和真实世界研究均予以证实。然而,目前可用的商业产品治疗后近半数患者仍会复发;多项CAR-T治疗前后的临床及生物学因素提示,在明确界定的患者中输注CAR-T后可能需要巩固治疗。这一发现表明,在将CAR-T适应证扩展至B-ALL首次复发及一线高危患者前,仍需解决诸多挑战:增强CAR-T细胞持续性以避免CD19阳性复发,并通过CAR-T输注前降低肿瘤负荷和/或多靶点策略避免CD19阴性复发。T细胞急性淋巴细胞白血病领域也正在出现具有令人鼓舞早期临床数据的有前景策略。由于缺乏白血病特异性抗原且存在免疫抑制性微环境,CAR-T细胞治疗急性髓系白血病仍面临挑战。
CAR T-cells therapy is seen as one of the most promising immunotherapies for leukemias, since targeting CD19 has revolutionized the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) in children, adolescents, and young adults. Early phase clinical trials have shown a very high initial response rate confirmed by follow up and real-world studies. However, almost half of patients relapse with the available commercial product currently suggesting the need of a consolidative treatment after CAR T-cell infusion in well-defined cases, according to several pre- and post-CAR clinical and biological factors. This finding highlights that numerous challenges exist before the extension of CAR T-cell indications (first relapse and high-risk first line) in the field of B-ALL: to enhance persistence of CAR T-cells to avoid CD19-positive relapse and to avoid CD19-negative relapse by reducing tumor burden pre-CAR-T infusion and/or by multitargeting. Promising approaches with exciting early clinical data are emerging in the field of T-cell ALL. The use of CAR T-cells for acute myeloid leukemias remains challenging due to the lack of leukemia-specific antigens and to the immunosuppressive microenvironment.
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