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:CD19 or CD20 CAR T Cell Therapy Demonstrates Durable Antitumor Efficacy in Patients with Central Nervous System Lymphoma.
CR的中位持续时间为22.4个月。
中枢神经系统(CNS)淋巴瘤患者预后较差。嵌合抗原受体修饰(CAR)T细胞对B细胞非霍奇金淋巴瘤显示出显著疗效。然而,很少有研究报道CAR T细胞治疗CNS淋巴瘤的效果,且缓解持续时间较短。在本研究中,7例CNS淋巴瘤患者(6例继发性CNS淋巴瘤和1例原发性CNS淋巴瘤)接受了CD19或CD20 CAR T细胞治疗,并评估了临床疗效和毒性特征。所有患者均对CAR T细胞治疗有应答。4例患者达到完全缓解(CR),3例表现为部分缓解。我们还发现,在4例患者的脑脊液中可检测到CD19或CD20 CAR T细胞。中位无进展生存期和中位总生存期未评估。中位CR持续时间为22.4个月。该队列中5例患者(5/7)接受了联合治疗(桥接自体造血干细胞移植和程序性死亡-1抑制剂维持治疗),3例患者(3/7)在CNS淋巴瘤复发后尽快接受了CAR T细胞治疗。这可能有助于解释这些患者为何获得长期缓解。在中位随访10.4个月后,3例患者出现疾病进展,其中1例患者确认CD20抗原丢失为复发原因。本研究结果表明,CD19或CD20 CAR T细胞对CNS淋巴瘤有效。本研究注册于http://www.chictr.org.cn(编号ChiCTR2000036350)。
Patients with central nervous system (CNS) lymphomas have a poor prognosis. Chimeric antigen receptor-modified (CAR) T cells have shown remarkable efficacy for B-cell non-Hodgkin's lymphoma. However, few studies have reported the effects of CAR T cells in the treatment of CNS lymphoma, and the duration of remission is short. In this study, seven CNS lymphoma patients (six patients with secondary CNS lymphomas and one patient with primary CNS lymphoma) were treated with CD19 or CD20 CAR T cell therapy, and the clinical efficacy and toxicity profiles were evaluated. All patients responded to CAR T cell therapy. Four patients achieved complete remission (CR), while three demonstrated partial remission. We also found that either CD19 or CD20 CAR T cells could be detected in the cerebrospinal fluid of four patients. The median progression-free survival and median overall survival were not assessed. The median duration of CR was 22.4 months. Five patients (5/7) in this cohort received combination therapy (bridging with autologous hematopoietic stem cell transplantation and programmed death-1 inhibitor for maintenance treatment) and three (3/7) received CAR T cell therapy as soon as possible after the relapse of CNS lymphoma. This could help explain why these patients achieved long-term remission. After a median follow-up of 10.4 months, three patients demonstrated disease progression, and the antigen loss of CD20 was confirmed as the reason for relapse in one patient. The results of this study suggest that CD19 or CD20 CAR T cells are effective against CNS lymphoma. This research was registered at http://www.chictr.org.cn (No. ChiCTR2000036350).
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