中文摘要
基于T细胞的细胞疗法最初获批用于淋巴系统恶性肿瘤(B细胞急性淋巴细胞白血病和大B细胞淋巴瘤),目前正在扩大对血液和非血液系统恶性肿瘤的研究及应用。近期,两种靶向B细胞成熟抗原(BCMA)的嵌合抗原受体(CAR)T细胞疗法获批用于复发/难治性多发性骨髓瘤,即使在经多线治疗的患者中也有出色疗效。这一新疗法显著改变了临床实践,但仍需进一步研究以优化抗原受体工程设计、细胞采集与筛选、治疗顺序等。此类疗法还会引起其他抗骨髓瘤治疗中少见的特有不良事件,尤其是细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS),因此需要专业经验进行管理和预防。其他基于T细胞的疗法,如TCR工程化T细胞,以及非基因工程化过继T细胞转移(Vγ9Vδ2 T细胞和骨髓浸润淋巴细胞),也在积极研究,值得关注。由于作用机制不同,它们有望在CAR-T 治疗失败后克服治疗难题。本文旨在向读者介绍多发性骨髓瘤T细胞疗法的临床数据、特有毒性的管理,以及临床和临床前研究进展。
展开英文摘要原文
T-cell-based cellular therapy was first approved in lymphoid malignancies (B-cell acute lymphoblastic leukemia and large B-cell lymphoma) and expanding its investigation and application both in hematological and non-hematological malignancies. Two anti-BCMA (B cell maturation antigen) CAR (Chimeric Antigen Receptor) T-cell therapies have been recently approved for relapsed and refractory multiple myeloma with excellent efficacy even in the heavily pre-treated patient population. This new therapeutic approach significantly changes our practice; however, there is still room for further investigation to optimize antigen receptor engineering, cell harvest/selection, treatment sequence, etc.
They are also associated with unique adverse events, especially CRS (cytokine release syndrome) and ICANS (immune effector cell-associated neurotoxicity syndrome), which are not seen with other anti-myeloma therapies and require expertise for management and prevention. Other T-cell based therapies such as TCR (T Cell Receptor) engineered T-cells and non-genetically engineered adoptive T-cell transfers (V 9 V 2 T-cells and Marrow infiltrating lymphocytes) are also actively studied and worth attention.
They can potentially overcome therapeutic challenges after the failure of CAR T-cell therapy through different mechanisms of action. This review aims to provide readers clinical data of T-cell-based therapies for multiple myeloma, management of unique toxicities and ongoing investigation in both clinical and pre-clinical settings.
论文信息
- 作者
- Simmons GL、Castaneda Puglianini O
- 第一作者单位
- Cellular Immunotherapies and Transplant Program, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.United States
- 通讯作者单位
- Department of Blood & Marrow Transplantation & Cellular Immunotherapy, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.United States
- 文献类型
- 综述
- 期刊
- Cancers2022 Aug 31