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:The evolving status of immunotherapies in multiple myeloma: the future role of bispecific antibodies.
The evolving status of immunotherapies in multiple myeloma: the future role of bispecific antibodies.
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过去10年中,多发性骨髓瘤(MM)的治疗结局已显著改善。然而,高危疾病患者,例如修订版国际分期系统III期疾病、存在不良细胞遗传学,或对蛋白酶体抑制剂、免疫调节药物和单克隆抗体难治的患者,其结局可能很差。这些患者代表着MM中一个亟待满足的持续需求。MM的特征之一是免疫功能障碍和允许肿瘤生长的免疫微环境。改善免疫麻痹可能带来更好的结局。免疫治疗的作用正以指数级速度增长,众多药物正在临床试验中开发。在本综述中,我们概述了MM中的免疫治疗,重点关注双特异性抗体(BsAbs)。我们回顾了已发表临床试验的疗效结局,并考虑了这些疗法的重要安全性方面,特别是细胞因子释放综合征和免疫效应细胞相关神经毒性综合征的风险,以及这些风险与接受CAR-T 细胞治疗患者的比较。我们讨论了BsAbs在临床或临床前阶段所靶向的MM表位,并思考这些疗法在未来不断变化的MM治疗范式中可能最适合的位置。
Treatment outcomes in multiple myeloma (MM) have improved dramatically over the past 10 years.
However, patients with high-risk disease such as those with Stage III disease by the Revised International Staging System, the presence of adverse cytogenetics, or who are refractory to proteosome inhibitors, immunomodulatory drugs and monoclonal antibodies may have dismal outcomes. These patients represent an urgent ongoing need in MM.
One of the hallmarks of MM is immune dysfunction and a tumour-permissive immune microenvironment. Ameliorating the immune-paresis could lead to improved outcomes. The role of immunotherapies has been growing at an exponential pace with numerous agents under development in clinical trials. In the present review, we provide an overview of immunotherapies in MM, focussing on bispecific antibodies (BsAbs).
We review efficacy outcomes from the published clinical trials and consider the important safety aspects of these therapies, in particular the risk of cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome, and how these compare with patients receiving chimeric antigen receptor T cells.
We discuss the MM epitopes being targeted by BsAbs, either in clinical or preclinical stages, and we consider where these therapies might best fit within the future ever-changing paradigm of MM treatment.
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