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

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‐m...

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Main Authors: An Zhu, Yu Bai, Yanyang Nan, Dianwen Ju
Format: Article
Language:English
Published: Wiley 2024-11-01
Series:Clinical and Translational Medicine
Subjects:
Online Access:https://doi.org/10.1002/ctm2.70046
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author An Zhu
Yu Bai
Yanyang Nan
Dianwen Ju
author_facet An Zhu
Yu Bai
Yanyang Nan
Dianwen Ju
author_sort An Zhu
collection DOAJ
description 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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spelling doaj-art-6f278796564e484fae63b2415e2bfbcc2024-12-05T05:48:38ZengWileyClinical and Translational Medicine2001-13262024-11-011411n/an/a10.1002/ctm2.70046Natural killer cell engagers: From bi‐specific to tri‐specific and tetra‐specific engagers for enhanced cancer immunotherapyAn Zhu0Yu Bai1Yanyang Nan2Dianwen Ju3Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy Shanghai ChinaDepartment of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy Shanghai ChinaDepartment of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy Shanghai ChinaDepartment of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy Shanghai ChinaAbstract 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.https://doi.org/10.1002/ctm2.70046bi‐specific NKCEscytokinesnatural killer cell engagersNK receptorstetra‐specific NKCEstri‐specific NKCEs
spellingShingle An Zhu
Yu Bai
Yanyang Nan
Dianwen Ju
Natural killer cell engagers: From bi‐specific to tri‐specific and tetra‐specific engagers for enhanced cancer immunotherapy
Clinical and Translational Medicine
bi‐specific NKCEs
cytokines
natural killer cell engagers
NK receptors
tetra‐specific NKCEs
tri‐specific NKCEs
title Natural killer cell engagers: From bi‐specific to tri‐specific and tetra‐specific engagers for enhanced cancer immunotherapy
title_full Natural killer cell engagers: From bi‐specific to tri‐specific and tetra‐specific engagers for enhanced cancer immunotherapy
title_fullStr Natural killer cell engagers: From bi‐specific to tri‐specific and tetra‐specific engagers for enhanced cancer immunotherapy
title_full_unstemmed Natural killer cell engagers: From bi‐specific to tri‐specific and tetra‐specific engagers for enhanced cancer immunotherapy
title_short Natural killer cell engagers: From bi‐specific to tri‐specific and tetra‐specific engagers for enhanced cancer immunotherapy
title_sort natural killer cell engagers from bi specific to tri specific and tetra specific engagers for enhanced cancer immunotherapy
topic bi‐specific NKCEs
cytokines
natural killer cell engagers
NK receptors
tetra‐specific NKCEs
tri‐specific NKCEs
url https://doi.org/10.1002/ctm2.70046
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