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:Case Report: Summary of multiple CAR-T expansions in anti-BCMA/GPRC5D bispecific CAR-T cell therapy for multiple myeloma.
靶向B细胞成熟抗原(BCMA)的嵌合抗原受体(CAR)-T细胞疗法已显示出显著疗效,被认为是治疗复发或难治性多发性骨髓瘤(R/R MM)的理想靶点。
靶向B细胞成熟抗原(BCMA)的嵌合抗原受体(CAR)-T细胞疗法已显示出显著疗效,被认为是治疗复发或难治性多发性骨髓瘤(R/R MM)的理想靶点。然而,由于BCMA表达不稳定或阴性,单靶点BCMA CAR-T细胞疗法仍面临挑战,而靶向G蛋白偶联受体C5家族成员D(GPRC5D)提供了新的治疗方向。临床研究表明,靶向GPRC5D的CAR-T细胞疗法对R/R MM具有较好的治疗潜力。本文报道了一例61岁男性R/R MM伴髓外病变(EMD)患者,该患者参加了一项抗BCMA/GPRC5D双特异性CAR-T细胞疗法的临床试验。输注后3个月,患者达到非常好的部分缓解(VGPR)。尽管患者经历了4次CAR-T细胞扩增并发生3级细胞因子释放综合征(CRS),但症状得到良好控制,治疗总体安全。本报告分析了4次CAR-T细胞扩增的原因,强调在抗BCMA/GPRC5D双特异性CAR-T细胞治疗期间需要密切监测和实验室检查。临床试验注册:本研究已在ClinicalTrials.gov注册,注册号为NCT06068400。
Chimeric antigen receptor (CAR) -T cell therapy targeting B-cell maturation antigen (BCMA) has demonstrated significant efficacy and is considered an ideal target for the treatment of relapsed or refractory multiple myeloma (R/R MM). However, due to the unstable or negative expression of BCMA, single-target BCMA CAR-T cell therapy still faces challenges, whereas targeting G protein-coupled receptor C5 family member D (GPRC5D) provides a new therapeutic direction. Clinical studies have shown that CAR-T cell therapy targeting GPRC5D has promising therapeutic potential for R/R MM. Here, this study is a case report on a 61-year-old male R/R MM patient with extramedullary disease (EMD) who participated in a clinical trial of anti-BCMA/GPRC5D bispecific CAR-T cell therapy. Three months after infusion, the patient achieved a very good partial response (VGPR). Although the patient experienced four episodes of CAR-T cell expansion and developed grade 3 cytokine release syndrome (CRS), the symptoms were well controlled, and the treatment demonstrated generally safe. Our report analyzes the reasons for the four CAR-T cell expansions, highlighting the need for close monitoring and laboratory testing during anti-BCMA/GPRC5D bispecific CAR-T cell therapy. Clinical trial registration: This study was registered on ClinicalTrials.gov, number NCT06068400.
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