文章：

Epcoritamab 对来自 DLBCL、FL 和 MCL 患者的恶性 B 细胞具有强效抗肿瘤活性，且不受既往 CD20 单抗治疗影响

Epcoritamab induces potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment

原文发布日期：2021-02-18

DOI: 10.1038/s41408-021-00430-6

类型: Article

开放获取: 是

英文摘要：

Epcoritamab (DuoBody-CD3xCD20, GEN3013) is a novel bispecific IgG1 antibody redirecting T-cells toward CD20+ tumor cells. Here, we assessed the preclinical efficacy of epcoritamab against primary tumor cells present in the lymph node biopsies from newly diagnosed (ND) and relapsed/refractory (RR) B-NHL patients. In the presence of T-cells from a healthy donor, epcoritamab demonstrated potent activity against primary tumor cells, irrespective of prior treatments, including CD20 mAbs. Median lysis of 65, 74, and 84% were achieved in diffuse large B-cell lymphoma (n = 16), follicular lymphoma (n = 15), and mantle cell lymphoma (n = 8), respectively. Furthermore, in this allogeneic setting, we discovered that the capacity of B-cell tumors to activate T-cells was heterogeneous and showed an inverse association with their surface expression levels of the immune checkpoint molecule Herpesvirus Entry Mediator (HVEM). In the autologous setting, when lymph node (LN)-residing T-cells were the only source of effector cells, the epcoritamab-dependent cytotoxicity strongly correlated with local effector cell-to-target cell ratios. Further analyses revealed that LN-residing-derived or peripheral blood-derived T-cells of B-NHL patients, as well as heathy donor T-cells equally mediated epcoritamab-dependent cytotoxicity. These results show the promise of epcoritamab for treatment of newly-diagnosed or relapsed/refractory B-NHL patients, including those who became refractory to previous CD20-directed therapies.
 

摘要翻译： 

Epcoritamab（DuoBody-CD3xCD20，GEN3013）是一种新型的双特异性IgG1抗体，能够引导T细胞靶向CD20阳性的肿瘤细胞。本研究评估了epcoritamab对初诊及复发/难治性B细胞非霍奇金淋巴瘤患者淋巴结活检中原代肿瘤细胞的临床前疗效。在健康供者T细胞存在的情况下，epcoritamab对原代肿瘤细胞表现出强大的活性，且不受既往治疗（包括CD20单抗）的影响。在弥漫性大B细胞淋巴瘤（n=16）、滤泡性淋巴瘤（n=15）和套细胞淋巴瘤（n=8）中，其中位细胞溶解率分别达到65%、74%和84%。此外，在这一异体环境中，我们发现B细胞肿瘤激活T细胞的能力具有异质性，且与其表面免疫检查点分子疱疹病毒入侵介体（HVEM）的表达水平呈负相关。在自体环境中，当淋巴结驻留T细胞是唯一的效应细胞来源时，epcoritamab依赖的细胞毒性与局部效应细胞-靶细胞的比例密切相关。进一步分析显示，B-NHL患者的淋巴结来源或外周血来源T细胞，以及健康供者的T细胞，均能同等介导epcoritamab依赖的细胞毒性。这些结果表明epcoritamab有望用于治疗初诊或复发/难治性B-NHL患者，包括那些对既往CD20靶向治疗产生耐药的患者。

原文链接：

Epcoritamab induces potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment