Natural killer cell engagers: From bi-specific to tri-specific and tetra-specific engagers for enhanced cancer immunotherapy

IF 7.9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Clinical and Translational Medicine Pub Date : 2024-10-29 DOI:10.1002/ctm2.70046

An Zhu, Yu Bai, Yanyang Nan, Dianwen Ju

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Abstract

Natural killer cell engagers (NKCEs) are a specialised subset of antibodies capable of simultaneously targeting endogenous NK cells and tumour cells, generating precise and effective cytolytic responses against cancer. This review systematically explores NK engagers as a rising star in NK-mediated immunotherapy, specifically focusing on multi-specific engagers. It examines the diverse configuration of NKCEs and how certain biologics could be employed to boost NK activity, including activating receptor engagement and cytokine incorporation. Some challenges and future perspectives of current NKCEs therapy are also discussed, including optimising pharmacokinetics, addressing the immunosuppressive tumour microenvironment and exploring potential combinatorial approaches. By offering an in-depth analysis of the current landscape and future trajectories of multi-specific NKCEs in cancer treatment, this review serves as a valuable resource for understanding this promising field of immunotherapy.

Highlights

Innovative NKCEs: NK cell engagers (NKCEs) represent a promising new class of immunotherapeutics targeting tumours by activating NK cells.
Multi-specific formats: The transition from bi-specific to multi-specific NKCEs enhances their versatility and therapeutic efficacy.
Mechanisms of action: NKCEs have the potential to improve NK cell activation by engaging activating receptors and incorporating cytokines.
Clinical potential: Current clinical trials demonstrate the safety and efficacy of various NKCEs across different cancer types.
Future research directions: Optimising NKCE designs and exploring combination therapies are essential for overcoming challenges in cancer treatment.

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自然杀伤细胞吸引器：从双特异性到三特异性和四特异性吸引剂，增强癌症免疫疗法。

自然杀伤细胞吞噬剂（NKCEs）是一种专门的抗体亚群，能够同时靶向内源性 NK 细胞和肿瘤细胞，产生精确有效的抗癌细胞溶解反应。这篇综述系统地探讨了作为 NK 介导的免疫疗法新星的 NK 接合剂，特别关注多特异性接合剂。它探讨了 NKCEs 的多种配置，以及如何利用某些生物制剂提高 NK 活性，包括激活受体参与和细胞因子结合。报告还讨论了当前 NKCEs 疗法面临的一些挑战和未来展望，包括优化药代动力学、解决免疫抑制性肿瘤微环境问题以及探索潜在的组合方法。本综述深入分析了多特异性 NKCEs 在癌症治疗中的现状和未来发展轨迹，是了解这一前景广阔的免疫疗法领域的宝贵资源：创新型 NKCE：NK细胞激活剂（NKCEs）是一类前景广阔的新型免疫疗法，它通过激活NK细胞来靶向治疗肿瘤。多特异性模式：从双特异性NKCE到多特异性NKCE的转变增强了它们的多功能性和疗效：NKCE具有通过激活受体和结合细胞因子改善NK细胞活化的潜力：目前的临床试验表明，各种 NKCEs 在不同癌症类型中均具有安全性和有效性。未来研究方向：优化 NKCE 设计和探索联合疗法对于克服癌症治疗中的挑战至关重要。

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来源期刊

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.