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T细胞衔接器——结构、功能原理及在血液系统恶性肿瘤中的应用

T-Cell Engagers-The Structure and Functional Principle and Application in Hematological Malignancies.

作者信息

Cech Paweł, Skórka Katarzyna, Dziki Laura, Giannopoulos Krzysztof

机构信息

Department of Experimental Hematooncology, Medical University of Lublin, 20-093 Lublin, Poland.

出版信息

Cancers (Basel). 2024 Apr 20;16(8):1580. doi: 10.3390/cancers16081580.

Abstract

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.

摘要

癌症免疫疗法的最新进展使得将细胞免疫反应导向癌细胞成为治疗血液系统恶性肿瘤的一种有前景的策略。基于单克隆抗体(mAbs)的靶向治疗的引入显著改善了血液系统疾病患者的预后。面对基于mAb治疗的问题,一种新型双特异性抗体(BsAb)形式被开发出来。T细胞衔接器(TCEs)是双特异性抗体,它同时靶向肿瘤细胞上的肿瘤相关抗原和T细胞上存在的CD3分子。这种机制允许直接激活T细胞及其抗肿瘤特性,最终导致肿瘤细胞裂解。2014年,美国食品药品监督管理局(FDA)批准了blinatumomab,一种靶向CD3和CD19的TCE,用于治疗急性淋巴细胞白血病。从那时起,许多TCEs被开发出来,可用于治疗不同的血液系统恶性肿瘤,如急性髓细胞白血病、多发性骨髓瘤、非霍奇金淋巴瘤和霍奇金淋巴瘤。截至2023年11月,有七种临床批准的基于TCE的疗法上市。基于TCE的疗法仍然有其局限性;然而,改善TCEs的特性,以及将基于TCE的疗法与其他治疗形式相结合,为找到目前晚期疾病的治愈方法带来了希望。在本文中,我们总结了TCE技术的技术基础、其在血液学中的应用以及其当前存在的问题和前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0dd/11048836/5ab509941ae2/cancers-16-01580-g001.jpg

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