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慢性淋巴细胞白血病和里希特综合征的细胞治疗进展。

Cellular Therapy Advances in Chronic Lymphocytic Leukemia and Richter's Syndrome.

机构信息

Division of Hospital Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.

Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.

出版信息

Curr Probl Cancer. 2022 Feb;46(1):100827. doi: 10.1016/j.currproblcancer.2021.100827. Epub 2021 Dec 25.

Abstract

Over the past 10 years, there have been great treatment advances for chronic lymphocytic leukemia (CLL) with the development of small molecule inhibitors. However, there remains an area of unmet need for patients who progress on novel therapies. The development of cellular therapies in CLL has been hindered by CLL induced immunosuppression. Fortunately, recent progress in various methods in immunomodulation may help overcome this limitation in CLL. These advances have spurred ongoing interest in the development of cellular therapies for CLL, including chimeric antigen receptor (CAR) T cell therapies, bi-specific antibodies, and use of natural killer cells. These novel treatment modalities may hold promise for patients with refractory, and potentially transformed disease. Here, we discuss the development of CAR-T cell therapy in CLL and the impact of combining CAR-T and small molecule inhibitors on treatment outcomes, the evolving role of bi-specific antibodies and natural killer cells, and comment on the use of cellular therapies for Richter's syndrome.

摘要

在过去的 10 年中,随着小分子抑制剂的发展,慢性淋巴细胞白血病(CLL)的治疗取得了重大进展。然而,对于新型疗法进展的患者,仍存在未满足的需求领域。CLL 诱导的免疫抑制阻碍了 CLL 中细胞疗法的发展。幸运的是,免疫调节的各种方法的最新进展可能有助于克服 CLL 中的这一限制。这些进展激发了对 CLL 细胞疗法的持续兴趣,包括嵌合抗原受体(CAR)T 细胞疗法、双特异性抗体以及自然杀伤细胞的应用。这些新的治疗方法可能为难治性和潜在转化疾病的患者带来希望。在这里,我们讨论了 CLL 中 CAR-T 细胞疗法的发展以及 CAR-T 和小分子抑制剂联合治疗对治疗结果的影响、双特异性抗体和自然杀伤细胞的作用不断变化,以及对 Richter 综合征中细胞疗法的应用进行了评论。

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