用于B细胞非霍奇金淋巴瘤的T细胞重定向疗法:近期进展与未来方向

T-cell redirecting therapies for B-cell non-Hodgkin lymphoma: recent progress and future directions.

作者信息

Russler-Germain David A, Ghobadi Armin

机构信息

Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States.

Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States.

出版信息

Front Oncol. 2023 Jul 3;13:1168622. doi: 10.3389/fonc.2023.1168622. eCollection 2023.

Abstract

Several key advances in the treatment of B-cell non-Hodgkin lymphoma (B-NHL) over the past two decades have strategically exploited B-cell lineage markers suitable for targeting by immunotherapies. First, the addition of the anti-CD20 monoclonal antibody (mAb) rituximab to a range of standard therapies conferred remarkable outcomes improvements in diverse settings, perhaps most prominently an overall survival advantage in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Subsequently, multiple chimeric antigen receptor (CAR) T-cell therapies targeting CD19 have revolutionized the treatment of relapsed/refractory (rel/ref) DLBCL and are active in other B-NHL subtypes as well. Most recently, the longstanding aspiration to exploit patients' endogenous T-cells to combat lymphoma has been achieved via T-cell redirecting therapies such as bispecific antibodies (BsAbs) that incorporate dual targeting of a T-cell antigen such as CD3 plus a B-cell antigen such as CD19 or CD20 expressed by the tumor. These novel agents have demonstrated impressive activity as monotherapies in patients with heavily pre-treated, rel/ref B-NHL of a variety of subtypes. Now, myriad clinical trials are exploring combinations of T-cell redirectors with targeted therapies, antibody-drug conjugates, conventional chemotherapy, and even new immunotherapies. Here, we highlight key landmarks in the development of T-cell redirecting therapies for the treatment of B-NHL, emerging evidence and lessons from recent clinical trials, and exciting new directions in this arena.

摘要

在过去二十年中,B细胞非霍奇金淋巴瘤(B-NHL)治疗方面的几项关键进展从战略上利用了适合免疫疗法靶向的B细胞谱系标志物。首先,在一系列标准疗法中添加抗CD20单克隆抗体(mAb)利妥昔单抗,在不同情况下都显著改善了治疗效果,或许最突出的是在新诊断的弥漫性大B细胞淋巴瘤(DLBCL)中具有总生存优势。随后,多种靶向CD19的嵌合抗原受体(CAR)T细胞疗法彻底改变了复发/难治性(rel/ref)DLBCL的治疗方式,并且在其他B-NHL亚型中也有活性。最近,通过双特异性抗体(BsAbs)等T细胞重定向疗法实现了利用患者内源性T细胞对抗淋巴瘤的长期愿望,这些双特异性抗体结合了对T细胞抗原(如CD3)和肿瘤表达的B细胞抗原(如CD19或CD20)的双重靶向。这些新型药物在多种亚型的重度预处理、rel/ref B-NHL患者中作为单药疗法已显示出令人印象深刻的活性。现在,无数临床试验正在探索T细胞重定向剂与靶向疗法、抗体药物偶联物、传统化疗甚至新免疫疗法的联合应用。在此,我们重点介绍用于治疗B-NHL的T细胞重定向疗法发展中的关键里程碑、近期临床试验的新证据和经验教训,以及该领域令人兴奋的新方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4833/10351267/5191ecf2fe07/fonc-13-1168622-g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索