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双特异性治疗:免疫检查点抑制联合共刺激与非检查点靶向治疗的前沿综述

英文原题:Bispecific therapeutics: a state-of-the-art review on the combination of immune checkpoint ‎inhibition with costimulatory and non-checkpoint targeted therapy.

查看英文原题

Bispecific therapeutics: a state-of-the-art review on the combination of immune checkpoint ‎inhibition with costimulatory and non-checkpoint targeted therapy.

PubMed 2024/11/18(内容时间) Expert Opin Biol Ther Q2 · IF 4(JCR 2025)

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研究概要

识别合适的靶点并选择有效的工程平台,增强了 bsAbs 应对 ICIs 等传统疗法相关挑战的潜力,使其成为癌症免疫治疗领域中一类有前景的治疗药物。

中文摘要

引言:免疫检查点抑制剂(ICI)彻底改变了癌症免疫治疗领域,并延长了恶性肿瘤患者的生存期。然而,ICI总体疗效仍不理想,且面临两大主要问题:耐药发生和免疫相关不良事件(irAE)。双特异性抗体(bsAb)凭借独特作用机制,已成为有前景的策略,有望比单克隆抗体(mAb)或其联合疗法取得更好疗效和安全性。bsAb以及其他双特异性平台(如双特异性融合蛋白、纳米抗体和CAR-T 细胞)可能有助于避免耐药,并减少mAb靶向结合肿瘤外组织所致的不良反应。 综述范围:我们在PubMed中检索英文文献,全面概述同时靶向免疫检查点和非检查点分子的bsAb这一增强型治疗药物类别的临床前和临床研究。 专家观点:确定合适靶点并选择有效工程化平台,可增强bsAb应对ICI等传统疗法相关挑战的潜力,使其成为癌症免疫治疗领域一类有前景的治疗药物。

展开英文摘要原文

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized the field of cancer immunotherapy and have enhanced the survival of patients with malignant tumors.

However, the overall efficacy of ICIs remains unsatisfactory and is faced with two major concerns of resistance development and occurrence of immune-related adverse events (irAEs). Bispecific antibodies (bsAbs) have emerged as promising strategies with unique mechanisms of action to achieve a better efficacy and safety than monoclonal antibodies (mAbs) or even their combination. BsAbs along with other bispecific platforms such as bispecific fusion proteins, nanobodies, and CAR-T cells may help to avoid development of resistance and reduce irAEs caused by on-target/off-tumor binding effects of mAbs.

AREAS COVERED: A literature search was performed using PubMed for English-language articles to provide a comprehensive overview of preclinical and clinical studies on bsAbs specified for both immune checkpoints and non-checkpoint molecules as a well-enhanced class of therapeutics.

EXPERT OPINION: Identifying suitable targets and selecting effective engineering platforms enhance the potential of bsAbs to address the challenges associated with conventional therapies such as ICIs, positioning them as a promising class of therapeutics in the landscape of cancer immunotherapy.

论文信息

作者
Mortaheb S、Pezeshki PS、Rezaei N
第一作者单位
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.Iran
通讯作者单位
Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.Iran
文献类型
综述
期刊
Expert opinion on biological therapy2024 Dec
原文标识
PubMed 39503381 · DOI 10.1080/14712598.2024.2426636