双特异性抗体和抗体药物偶联物在复发/难治性侵袭性非霍奇金淋巴瘤中的应用,重点关注弥漫性大B细胞淋巴瘤
Bispecific Antibodies and Antibody-Drug Conjugates in Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma, Focusing on Diffuse Large B-Cell Lymphoma.
作者信息
Caserta Santino, Campo Chiara, Cancemi Gabriella, Neri Santo, Stagno Fabio, Mannina Donato, Allegra Alessandro
机构信息
Hematology Unit, Department of Human Pathology in Adulthood and Childhood "Gaetano Barresi", University of Messina, Via Consolare Valeria, 98125 Messina, Italy.
Hematology Unit, Oncology-Hematology Department, Azienda Ospedaliera Papardo, 98158 Messina, Italy.
出版信息
Cancers (Basel). 2025 Jul 26;17(15):2479. doi: 10.3390/cancers17152479.
Relapsed/refractory diffuse large B-cell lymphoma and other non-Hodgkin lymphomas represent significant clinical challenges, particularly in patients who have exhausted standard immunochemotherapy and cellular therapies. Bispecific antibodies and antibody-drug conjugates have emerged as promising treatments, offering targeted and more effective treatment options compared to current standards. Bispecific antibodies, including epcoritamab and glofitamab, third-line therapies for diffuse large B-cell lymphoma, are recombinant immunoglobulins engineered to recognize two distinct antigens or epitopes simultaneously. This capability enhances therapeutic precision by bridging immune effector cells and tumor cells and modulating multiple signaling pathways involved in the pathogenesis of non-Hodgkin lymphoma. In the context of new therapies, antibody-drug conjugates, such as loncastuximab tesirine, are therapies composed of monoclonal antibodies linked to cytotoxic agents, in which the antibody selectively binds to tumor-associated antigens, delivering the cytotoxic payload directly to cancer cells while minimizing off-target effects. They combine the specificity of antibodies with the potency of chemotherapy, offering enhanced efficacy and safety in hematological malignancies. Ongoing clinical trials are investigating other molecules like odronextamab and the use of bispecific antibodies in combination regimens and earlier lines of therapy. The aim of this review is to explore actual therapies in relapsed/refractory diffuse large B-cell lymphoma, focusing on bispecific antibodies and antibody-drug conjugates.
复发/难治性弥漫性大B细胞淋巴瘤和其他非霍奇金淋巴瘤是重大的临床挑战,尤其对于那些已用尽标准免疫化疗和细胞疗法的患者。双特异性抗体和抗体药物偶联物已成为有前景的治疗方法,与当前标准相比,提供了更具针对性和更有效的治疗选择。双特异性抗体,包括用于弥漫性大B细胞淋巴瘤的三线疗法艾可瑞妥单抗和格罗菲妥单抗,是经过工程改造以同时识别两种不同抗原或表位的重组免疫球蛋白。这种能力通过桥接免疫效应细胞和肿瘤细胞并调节非霍奇金淋巴瘤发病机制中涉及的多种信号通路来提高治疗精度。在新疗法方面,抗体药物偶联物,如洛卡斯妥单抗,是由与细胞毒性药物连接的单克隆抗体组成的疗法,其中抗体选择性地结合肿瘤相关抗原,将细胞毒性载荷直接递送至癌细胞,同时将脱靶效应降至最低。它们将抗体的特异性与化疗的效力相结合,在血液系统恶性肿瘤中提供更高的疗效和安全性。正在进行的临床试验正在研究其他分子,如奥多奈单抗,以及双特异性抗体在联合治疗方案和更早治疗线中的应用。本综述的目的是探讨复发/难治性弥漫性大B细胞淋巴瘤的实际治疗方法,重点关注双特异性抗体和抗体药物偶联物。