4.3 Review

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

Journal

MOLECULAR DIAGNOSIS & THERAPY
Volume 25, Issue 5, Pages 577-592

Publisher

ADIS INT LTD
DOI: 10.1007/s40291-021-00550-6

Keywords

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Funding

  1. US Department of Defense [PC190189, NCI P01 CA111412, R35 CA197292]

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NK cell-mediated cancer immunotherapy has made significant advancements in the past two decades, with the development of multi-specific engagers effectively arming NK cells to induce specific cytolytic responses against tumor targets. These engagers have shown compelling potential in boosting NK cell cytotoxicity against specific tumor targets.
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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