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重新构想癌症中的抗体依赖性细胞介导的细胞毒性作用:NK 细胞衔接器的潜力

英文原题:Reimagining antibody-dependent cellular cytotoxicity in cancer: the potential of natural killer cell engagers.

查看英文原题

Reimagining antibody-dependent cellular cytotoxicity in cancer: the potential of natural killer cell engagers.

PubMed 2022/11/01(内容时间) Trends Immunol Q1 · IF 13.1(JCR 2025)

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中文摘要

双特异性、三特异性和多特异性抗体使得靶向癌症免疫疗法得以发展,这些疗法能够重定向免疫效应细胞以消除恶性转化的细胞。这些抗体能够同时结合恶性细胞表面的抗原以及固有免疫细胞(如自然杀伤(NK)细胞、巨噬细胞和中性粒细胞)上的激活性受体。此类抗体已取得重大进展,尤其是在血液系统恶性肿瘤方面。然而,仍存在若干重大挑战,包括在更大比例的患者中提高其免疫治疗疗效,特别是在携带实体瘤的患者中,以及克服剂量限制性毒性和免疫原性。在此,我们讨论旨在通过NK细胞衔接器介导抗体依赖性细胞介导的细胞毒性(ADCC)来最大化NK细胞潜力的新型抗体工程进展,从而扩展癌症免疫治疗的武器库。

展开英文摘要原文

Bi-, tri- and multispecific antibodies have enabled the development of targeted cancer immunotherapies redirecting immune effector cells to eliminate malignantly transformed cells. These antibodies allow for simultaneous binding of surface antigens on malignant cells and activating receptors on innate immune cells, such as natural killer (NK) cells, macrophages, and neutrophils.

Significant progress with such antibodies has been achieved, particularly in hematological malignancies. Nevertheless, several major challenges remain, including increasing their immunotherapeutic efficacy in a greater proportion of patients, particularly in those harboring solid tumors, and overcoming dose-limiting toxicities and immunogenicity.

Here, we discuss novel antibody-engineering developments designed to maximize the potential of NK cells by NK cell engagers mediating antibody-dependent cellular cytotoxicity (ADCC), thereby expanding the armamentarium for cancer immunotherapy.

论文信息

作者
Pinto S、Pahl J、Schottelius A、Carter PJ、Koch J
第一作者单位
Affimed GmbH, Heidelberg, Germany.Germany
通讯作者单位
Affimed GmbH, Heidelberg, Germany. Electronic address: J.Koch@affimed.com.Germany
文献类型
综述
期刊
Trends in immunology2022 Nov
原文标识
PubMed 36306739 · DOI 10.1016/j.it.2022.09.007