CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CAR-T cells for the treatment of relapsed/refractory multiple myeloma in 2022: efficacy and toxicity.
CAR-T cells for the treatment of relapsed/refractory multiple myeloma in 2022: efficacy and toxicity.
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嵌合抗原受体(CAR)-T细胞是包括复发/难治性多发性骨髓瘤(RRMM)在内的多种血液系统恶性肿瘤的一种新治疗方式。RRMM患者预后差,治疗选择有限。目前来自CAR-T 细胞治疗临床试验的可用数据已证明其在RRMM中具有疗效且毒性可控。RRMM中的CAR-T 细胞大多集中于已知的细胞靶点,如B细胞成熟抗原(BCMA)。针对其他靶点的CAR-T 细胞也已在多项临床试验中进行分析。细胞因子释放综合征(CRS)、特异性神经毒性和血液学毒性是主要不良事件(AE);根据临床试验,它们大多为轻度,3级或以上毒性的发生率较低。针对BCMA的自体CAR-T 细胞疗法(ide-cel和cilta-cel)显示出最佳疗效,在RRMM中具有总体缓解率和中位无进展生存期。ide-cel和cilta-cel均已获得FDA批准。目前,CAR-T 细胞常规应用的主要争议是高昂的治疗成本和未知的长期疗效。在这篇综述中,我们总结了2021年RRMM中CAR-T 细胞疗法的当前概况,包括CAR-T 细胞的各种靶点及其疗效、安全性和可能的局限性。未来需要前瞻性临床试验来阐明CAR-T 细胞在MM治疗中的最佳作用。
Chimeric antigen receptor (CAR)-T cells are a new treatment modality in various hematological malignancies, including relapsed/refractory multiple myeloma (RRMM). RRMM patients have a poor prognosis, and their treatment options are limited. Currently available data from clinical trials on CAR-T cell therapy have demonstrated efficacy and manageable toxicity in RRMM. The CAR-T cells in RRMM mostly focus on already known cellular targets, such as B-cell maturation antigen (BCMA). CAR-T cells focusing on other targets have been analyzed in various clinical trials as well. Cytokine release syndrome (CRS), specific neurotoxicity, and hematological toxicity are the main adverse events (AE); according to the clinical trials, they are mostly mild with a low incidence of grade 3 or higher toxicities.
The autologous CAR-T cell therapy against BCMA (ide-cel and cilta-cel) shows the best efficacy with an overall response rate and a median progression-free survival in RRMM. Both ide-cel and cilta-cel have already been approved by the FDA. Currently, the main controversies in the routine use of CAR-T cells are high treatment costs and unknown long-term efficacy.
In this review, we summarize the current overview of CAR-T cell therapies in RRMM in 2021 with various targets for CAR-T cells and their efficacy, safety, and possible limitations. Future prospective clinical trials are needed to clarify the optimal role of CAR-T cells in MM therapy.
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