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实体瘤的T细胞接合疗法。

T-cell-engaging Therapy for Solid Tumors.

作者信息

de Miguel Maria, Umana Pablo, Gomes de Morais Ana Luiza, Moreno Victor, Calvo Emiliano

机构信息

START Madrid-HM Centro Integral Oncológico Clara Campal (CIOCC) Early Phase Program, HM Sanchinarro University Hospital, Madrid, Spain.

Roche Innovation Center Zurich Schlieren, Zurich, Switzerland.

出版信息

Clin Cancer Res. 2021 Mar 15;27(6):1595-1603. doi: 10.1158/1078-0432.CCR-20-2448. Epub 2020 Oct 20.

DOI:10.1158/1078-0432.CCR-20-2448
PMID:33082210
Abstract

T-cell engagers (TCE) are a rapidly evolving novel group of treatments that have in common the concurrent engagement of a T-cell surface molecule and a tumoral cell antigen. Bispecific antibodies and genetically engineered adoptive cell therapies, as chimeric antigen receptors or T-cell receptors, have similarities and differences among their mechanisms of action, toxicity profiles, and resistance pathways. Nevertheless, the success observed in the hematologic field has not been obtained with solid tumors yet, as they are biologically more complex and have few truly tumor-specific cell surface antigens that can be targeted with high avidity T cells. Different strategies are under study to improve their short-term perspective, such as new generations of more active TCEs, multi-target or combination of different treatments approaches, or to improve the manufacturing processes. A comprehensive review of TCEs as a grouped treatment class, their current status, and research directions in their application to solid tumors therapeutics are discussed here.

摘要

T细胞衔接器(TCE)是一类迅速发展的新型治疗药物,它们的共同特点是同时结合T细胞表面分子和肿瘤细胞抗原。双特异性抗体和基因工程过继性细胞疗法,如嵌合抗原受体或T细胞受体,在作用机制、毒性特征和耐药途径方面既有相似之处,也有不同之处。然而,在血液学领域观察到的成功尚未在实体瘤中实现,因为实体瘤在生物学上更为复杂,几乎没有真正的肿瘤特异性细胞表面抗原可供高亲和力T细胞靶向。目前正在研究不同的策略来改善其短期前景,例如新一代更具活性的TCE、多靶点或不同治疗方法的联合应用,或者改进制造工艺。本文将对作为一类联合治疗药物的TCE、其现状以及在实体瘤治疗中的研究方向进行全面综述。

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