文章：

血液系统恶性肿瘤中的双特异性抗体：一项范围综述

Bispecific Antibodies in Hematological Malignancies: A Scoping Review

原文发布日期：14 September 2023

DOI: 10.3390/cancers15184550

类型: Article

开放获取: 是

英文摘要：

Bispecific T-cell engagers (BiTEs) and bispecific antibodies (BiAbs) have revolutionized the treatment landscape of hematological malignancies. By directing T cells towards specific tumor antigens, BiTEs and BiAbs facilitate the T-cell-mediated lysis of neoplastic cells. The success of blinatumomab, a CD19xCD3 BiTE, in acute lymphoblastic leukemia spearheaded the expansive development of BiTEs/BiAbs in the context of hematological neoplasms. Nearly a decade later, numerous BiTEs/BiAbs targeting a range of tumor-associated antigens have transpired in the treatment of multiple myeloma, non-Hodgkin’s lymphoma, acute myelogenous leukemia, and acute lymphoblastic leukemia. However, despite their generally favorable safety profiles, particular toxicities such as infections, cytokine release syndrome, myelosuppression, and neurotoxicity after BiAb/BiTE therapy raise valid concerns. Moreover, target antigen loss and the immunosuppressive microenvironment of hematological neoplasms facilitate resistance towards BiTEs/BiAbs. This review aims to highlight the most recent evidence from clinical trials evaluating the safety and efficacy of BiAbs/BiTEs. Additionally, the review will provide mechanistic insights into the limitations of BiAbs whilst outlining practical applications and strategies to overcome these limitations.

摘要翻译： 

双特异性T细胞衔接器（BiTEs）与双特异性抗体（BiAbs）已彻底改变了血液系统恶性肿瘤的治疗格局。通过引导T细胞靶向特定肿瘤抗原，BiTEs与BiAbs促进T细胞介导的肿瘤细胞裂解。以CD19xCD3双特异性T细胞衔接器贝林妥欧单抗在急性淋巴细胞白血病治疗中的成功为先导，BiTEs/BiAbs在血液肿瘤领域的研发应用得到广泛拓展。近十年来，针对多种肿瘤相关抗原的BiTEs/BiAbs已相继应用于多发性骨髓瘤、非霍奇金淋巴瘤、急性髓系白血病及急性淋巴细胞白血病的临床治疗。然而，尽管这类药物总体安全性良好，但其治疗引发的特定毒性反应——如感染、细胞因子释放综合征、骨髓抑制及神经毒性——仍值得关注。此外，靶抗原丢失及血液肿瘤的免疫抑制微环境也导致了对BiTEs/BiAbs的耐药性。本综述旨在重点阐述评估BiAbs/BiTEs安全性与有效性的临床试验最新证据，同时从机制层面解析BiAbs的局限性，并概述克服这些局限性的实际应用策略。

原文链接：

Bispecific Antibodies in Hematological Malignancies: A Scoping Review