Saleh Khalil, Khoury Rita, Khalife Nadine, Chahine Claude, Ibrahim Rebecca, Tikriti Zamzam, Le Cesne Axel
International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France.
Department of Head and Neck Oncology, Gustave Roussy Cancer Campus, 94800 Villejuif, France.
J Pers Med. 2024 Jun 21;14(7):666. doi: 10.3390/jpm14070666.
The advent of targeted therapies such as monoclonal antibodies, adoptive T-cell therapies, and antibody-drug conjugates (ADCs) dramatically changed the treatment landscape of diffuse large B-cell lymphoma (DLBCL) over the last two decades. Rituximab was the first one approved. Chimeric antigen receptor T-cells are currently approved as second-line treatment in patients with DLBCL refractory to first-line chemo-immunotherapy. Polatuzumab, a CD79b-targeting ADC, is approved as first-line treatment in high-risk patients in combination with chemo-immunotherapy. Bispecific antibodies (BsAbs) are a novel category of drugs that are also changing the treatment paradigm of patients with DLBCL. They are engineered to bind to two different targets at the same time. To date, two BsAbs (glofitamab and epcoritamab) are approved as monotherapy in third-line treatment in DLBCL. Combination strategies with chemotherapy, immunotherapy, and ADCs are currently under investigation with encouraging results in first-line or subsequent lines of treatment. In the following review, we focus on the structure of BsAbs, the mechanism of action, clinical efficacy, and the mechanisms of resistance to BsAbs.
在过去二十年中，单克隆抗体、过继性T细胞疗法和抗体药物偶联物（ADC）等靶向疗法的出现极大地改变了弥漫性大B细胞淋巴瘤（DLBCL）的治疗格局。利妥昔单抗是首个获批的药物。嵌合抗原受体T细胞目前被批准用于一线化疗免疫疗法难治的DLBCL患者的二线治疗。泊洛妥珠单抗是一种靶向CD79b的ADC，被批准用于高危患者与化疗免疫疗法联合的一线治疗。双特异性抗体（BsAb）是一类新型药物，也正在改变DLBCL患者的治疗模式。它们被设计为可同时结合两个不同靶点。迄今为止，两种BsAb（格菲妥单抗和依泊妥单抗）被批准用于DLBCL三线治疗的单药治疗。目前正在研究BsAb与化疗、免疫疗法和ADC的联合策略，在一线或后续治疗中取得了令人鼓舞的结果。在以下综述中，我们将重点关注BsAb的结构、作用机制、临床疗效以及对BsAb的耐药机制。
