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双特异性抗体在癌症治疗中的现状与未来

英文原题:The present and future of bispecific antibodies for cancer therapy.

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The present and future of bispecific antibodies for cancer therapy.

PubMed 2024/03/06(内容时间) Nat Rev Drug Discov Q1 · IF 91.2(JCR 2025)

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中文摘要

双特异性抗体(bsAbs)能够实现传统基于IgG的抗体无法达成的新作用机制和/或治疗应用。因此,过去十年间这类分子的开发引起了极大关注,截至2023年底,已有14种bsAbs获批:11种用于癌症治疗,3种用于非肿瘤适应症。bsAbs存在不同形式,靶向不同目标,并通过不同分子机制介导抗肿瘤功能。在此,我们概述了bsAbs在癌症治疗领域的最新进展。我们重点关注已获批或处于临床开发阶段的bsAbs,包括bsAb介导的信号通路双重调节剂、肿瘤靶向受体激动剂、bsAb-药物偶联物、双特异性T细胞、NK 细胞和先天免疫细胞衔接器,以及双特异性检查点抑制剂和共刺激因子。最后,我们展望了处于早期开发阶段的下一代bsAbs,包括三特异性抗体、bsAb前药、诱导肿瘤靶点降解的bsAbs以及作为细胞因子模拟物的bsAbs。

展开英文摘要原文

Bispecific antibodies (bsAbs) enable novel mechanisms of action and/or therapeutic applications that cannot be achieved using conventional IgG-based antibodies. Consequently, development of these molecules has garnered substantial interest in the past decade and, as of the end of 2023, 14 bsAbs have been approved: 11 for the treatment of cancer and 3 for non-oncology indications. bsAbs are available in different formats, address different targets and mediate anticancer function via different molecular mechanisms.

Here, we provide an overview of recent developments in the field of bsAbs for cancer therapy.

We focus on bsAbs that are approved or in clinical development, including bsAb-mediated dual modulators of signalling pathways, tumour-targeted receptor agonists, bsAb-drug conjugates, bispecific T cell, natural killer cell and innate immune cell engagers, and bispecific checkpoint inhibitors and co-stimulators.

Finally, we provide an outlook into next-generation bsAbs in earlier stages of development, including trispecifics, bsAb prodrugs, bsAbs that induce degradation of tumour targets and bsAbs acting as cytokine mimetics.

论文信息

作者
Klein C、Brinkmann U、Reichert JM、Kontermann RE
第一作者单位
Roche Pharma Research and Early Development, Roche Innovation Center Zurich, Schlieren, Switzerland. christian.klein.ck1@roche.com.Switzerland
通讯作者单位
Institute of Cell Biology and Immunology, University Stuttgart, Stuttgart, Germany. roland.kontermann@izi.uni-stuttgart.de.Germany
文献类型
综述
期刊
Nature reviews. Drug discovery2024 Apr
原文标识
PubMed 38448606 · DOI 10.1038/s41573-024-00896-6