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. 2024 Aug 29;16(9):1143. doi: 10.3390/pharmaceutics16091143

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© 2024 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Schematic representation of the key NK-cell-NK-cell-based strategies for cancer immunotherapy. (1) Overexpression of surface-activating receptors for enhanced cell activation and cancer antigen recognition. CD16 overexpression to boost the antibody-dependent cellular cytotoxicity (ADCC) function in combination with therapeutic monoclonal antibodies (mAbs). (2) Blockade of inhibitory receptor interaction with their ligands to ignite NK cell cytotoxicity using immune checkpoint inhibitors (ICIs). (3) Adoptive cell transfer (ACT) of modified NK cells with chimeric antigen receptor (CAR) constructs with or without the simultaneous overexpression of receptor repertoire. (4) Cytokine administration and modified NK cells to endogenously express cytokines for enhanced stimulation. (5) Use of bi- and tri-specific killer engagers for the simultaneous targeting/linking of NK cell receptors and tumor-associated antigens. (6) NK cell chemotactic receptor activation for tumor site migration and subsequent infiltration. Created with BioRender.