Recent advancements in cancer immunotherapy have made directing the cellular immune response onto cancer cells a promising strategy for the treatment of hematological malignancies. The introduction of monoclonal antibody-based (mAbs) targeted therapy has significantly improved the prognosis for hematological patients. Facing the issues of mAb-based therapies, a novel bispecific antibody (BsAb) format was developed. T-cell engagers (TCEs) are BsAbs, which simultaneously target tumor-associated antigens on tumor cells and CD3 molecules present on T-cells. This mechanism allows for the direct activation of T-cells and their anti-tumor features, ultimately resulting in the lysis of tumor cells. In 2014, the FDA approved blinatumomab, a TCE directed to CD3 and CD19 for treatment of acute lymphoblastic leukemia. Since then, numerous TCEs have been developed, allowing for treating different hematological malignancies such as acute myeloid leukemia, multiple myeloma, and non-Hodgkin lymphoma and Hodgkin lymphoma. As of November 2023, seven clinically approved TCE therapies are on the market. TCE-based therapies still have their limitations; however, improving the properties of TCEs, as well as combining TCE-based therapies with other forms of treatment, give hope to find the cures for currently terminal diseases. In this paper, we summarized the technical basis of the TCE technology, its application in hematology, and its current issues and prospects.
近年来，癌症免疫治疗领域的进展使得引导细胞免疫应答靶向癌细胞成为治疗血液系统恶性肿瘤的重要策略。基于单克隆抗体的靶向治疗显著改善了血液病患者的预后。为应对单抗疗法存在的局限性，新型双特异性抗体应运而生。T细胞衔接器作为双特异性抗体的一种，能同时靶向肿瘤细胞表面的肿瘤相关抗原和T细胞表面的CD3分子。该机制可直接激活T细胞并增强其抗肿瘤特性，最终导致肿瘤细胞裂解。2014年，美国食品药品监督管理局批准了首个靶向CD3和CD19的T细胞衔接器——贝林妥欧单抗，用于治疗急性淋巴细胞白血病。此后，多种T细胞衔接器相继问世，为急性髓系白血病、多发性骨髓瘤、非霍奇金淋巴瘤及霍奇金淋巴瘤等血液系统恶性肿瘤提供了新的治疗选择。截至2023年11月，已有七种T细胞衔接器疗法获临床批准上市。尽管该疗法仍存在局限性，但通过优化T细胞衔接器的特性，并将其与其他治疗方式联合应用，有望为当前无法治愈的疾病找到解决方案。本文系统综述了T细胞衔接器技术的理论基础、在血液学领域的应用现状以及当前面临的挑战与发展前景。
T-Cell Engagers—The Structure and Functional Principle and Application in Hematological Malignancies
肿瘤(癌症)患者之家