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Bi-specific and Tri-specific NK Cell Engagers: The New Avenue of Targeted NK Cell Immunotherapy

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Abstract

Natural killer (NK) cell-mediated cancer immunotherapy has grown significantly over the past two decades. More recently, multi-specific engagers have been developed as cancer therapeutics to effectively arm endogenous NK cells to more potently induce specific cytolytic responses against tumor targets. This review explores the bi- and tri-specific NK/tumor engagers that are emerging as a new generation of immunotherapeutics. These molecules vary in configuration, but they typically have small molecular weights and domains that engage specific tumor antigens and NK cell-activating receptors such as CD16, NKp30, NKp46, and NKG2D. They have demonstrated compelling potential in boosting NK cell cytotoxicity against specific tumor targets. This highly adaptable off-the-shelf platform, which in some formats also integrates cytokines, is poised to revolutionize targeted NK cell immunotherapy, either as a monotherapy or in combination with other effective anti-cancer therapies.

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  1. Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    Shee Kwan Phung, Jeffrey S. Miller & Martin Felices

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  1. Shee Kwan Phung
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Correspondence to Martin Felices.

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This work was supported, in part, by US Department of Defense PC190189, NCI P01 CA111412 and R35 CA197292.

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Dr. Felices and Dr. Miller receive consulting honoraria, royalties and/or own stock from GT Biopharma, who licenses the TriKETM platform from the University of Minnesota. These interests have been reviewed and managed by the University of Minnesota in accordance with its conflict-of-interest policy.

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SKP wrote and edited manuscript; JSM and MF supervised, reviewed, wrote, and organized manuscript.

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Phung, S.K., Miller, J.S. & Felices, M. Bi-specific and Tri-specific NK Cell Engagers: The New Avenue of Targeted NK Cell Immunotherapy. Mol Diagn Ther 25, 577–592 (2021). https://doi.org/10.1007/s40291-021-00550-6

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