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REVIEW article

Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1483884
This article is part of the Research Topic Advancements in Drug Development: Exploring Bi-Specific Antibodies as Promising Therapeutic Strategies in Oncology View all articles

The Horizon of Natural Killer Cell Engagers for Cancer Immunotherapy

Provisionally accepted
Shahryar Khoshtinat Nikkhoi Shahryar Khoshtinat Nikkhoi Geng Li Geng Li Arash Hatefi Arash Hatefi *
  • Rutgers, The State University of New Jersey - Busch Campus, Piscataway, United States

The final, formatted version of the article will be published soon.

    This review article explores the rapidly evolving field of bi-, tri-, and multi-specific NK cell engagers (NKCEs), highlighting their potential as a cutting-edge approach in cancer immunotherapy. NKCEs offer a significant advancement over conventional monoclonal antibodies (mAbs) by enhancing Antibody-Dependent Cellular Cytotoxicity (ADCC). They achieve this by stably and selectively binding to both NK cell activating receptors and tumorassociated antigens (TAAs). Unlike traditional mAbs, which depend on the relatively transient interaction between their Fc region and CD16a, NKCEs establish more robust connections with a range of activating receptors (e.g., CD16a, NKG2D, NKp30, NKp46, NKG2C) and inhibitory receptors (e.g., Siglec-7) on NK cells, thereby increasing cancer cell killing efficacy and specificity. This review article critically examines the strategies for engineering bi-, tri-, and multispecific NKCEs for cancer immunotherapy, providing an in-depth analysis of the latest advancements in NKCE platform technologies currently under development by pharmaceutical and biotech companies and discussing the preclinical and clinical progress of these products. While NKCEs show great promise, the review underscores the need for continued research to optimize their therapeutic efficacy and to overcome obstacles related to NK cell functionality in cancer patients. Ultimately, this article presents an overview of the current landscape and future prospects of NKCE-based cancer immunotherapy, emphasizing its potential to revolutionize cancer treatment.

    Keywords: NKCE platform technologies, NK activating receptors, bispecifc trispecific multispecific antibodies, CD16a NKG2D NKG2C NKp30 NKp46, cancer immunotherapy, Natural killer cells (NK cells)

    Received: 20 Aug 2024; Accepted: 31 Dec 2024.

    Copyright: © 2024 Nikkhoi, Li and Hatefi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Arash Hatefi, Rutgers, The State University of New Jersey - Busch Campus, Piscataway, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.