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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Emerging Targets and Cellular Therapy for Relapsed Refractory Multiple Myeloma: A Systematic Review.
Emerging Targets and Cellular Therapy for Relapsed Refractory Multiple Myeloma: A Systematic Review.
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多发性骨髓瘤是第二常见的血液系统恶性肿瘤,目前仍无法治愈。尽管骨髓瘤治疗近期取得进展,但多线治疗失败的患者预后通常仍较差。CAR-T(CAR-T)细胞治疗已成为多种血液系统恶性肿瘤的潜在疗法,近期也获批用于骨髓瘤,且仍有新的适应证在开发中。
我们系统综述了现有CAR-T 治疗多发性骨髓瘤的临床试验数据。我们检索了ClinicalTrials.gov上全部多发性骨髓瘤临床试验,纳入提及CAR-T 且研究复发/难治性多发性骨髓瘤(R/R MM)的研究,并查阅PubMed、Google Scholar和会议论文集,以确认哪些试验已报告数据。截至2021年3月10日,共找到27项已发表数据的人体注册临床试验。大多数试验采用靶向B细胞成熟抗原(BCMA)的CAR-T 细胞,且许多为I期研究。数据表明,短期(<12个月)疗效令人鼓舞,3级及以上毒性发生率较低。CAR-T 细胞治疗仍是R/R MM的一种有前景的治疗方式。一种生物制剂近期已获FDA批准,但大多数产品仍处于研究阶段或早期临床试验阶段。仍需进一步研究,以确定如何优化CAR-T 构建体和联合治疗方案,从而改善患者结局。
Multiple myeloma is the second most common hematologic malignancy and remains incurable. Patients who fail multiple lines of therapy typically have a poor prognosis despite recent advances in myeloma treatment. Chimeric antigen receptor T (CAR T) cell treatment has emerged as a promising therapy for many hematologic malignancies, including recently approved and emerging applications for myeloma treatment. A systematic review of the available clinical trial data for CAR T therapies in multiple myeloma was undertaken. All multiple myeloma trials registered at ClinicalTrials. gov were reviewed and studies mentioning CAR T and studying relapsed/refractory multiple myeloma (R/R MM) were included.
PubMed, Google Scholar, and conference proceedings were also reviewed to determine which trials had reported data. Twenty-seven registered clinical trials in humans with published data were identified as of March 10, 2021. The majority of these trials were CAR T cells targeting B-cell maturation antigen (BCMA), and many were Phase I studies.
Data demonstrated promising short-term (<12 months) efficacy with low incidence of grade 3 or higher toxicities. CAR T cell therapy in R/R MM remains a promising treatment modality. While one biologic has recently received FDA-approval, the majority of products remain investigational and in early-phase trials. More investigation is needed to determine which CAR T constructs and combination therapies optimize patient outcomes.
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