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

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24 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)577-592
Number of pages16
JournalMolecular Diagnosis and Therapy
Issue number5
StatePublished - Sep 2021

Bibliographical note

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

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.


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