Modulation of intrinsic inhibitory checkpoints using nano‐carriers to unleash NK cell activity

Modulation of intrinsic inhibitory checkpoints using nano‐carriers to unleash NK cell activity

Abstract Natural killer (NK) cells provide a powerful weapon mediating immune defense against viral infections, tumor growth, and metastatic spread. NK cells demonstrate great potential for cancer immunotherapy; they can rapidly and directly kill cancer cells in the absence of MHC‐dependent antigen...

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Bibliographic Details
Main Authors: Guy Biber, Batel Sabag, Anat Raiff, Aviad Ben‐Shmuel, Abhishek Puthenveetil, Jennifer I C Benichou, Tammir Jubany, Moria Levy, Shiran Killner, Mira Barda‐Saad
Format: Article
Language:English
Published: Springer Nature 2021-11-01
Series:EMBO Molecular Medicine
Subjects:
Cbl
immunotherapy
nanoparticles
NK cells
SHP‐1
Online Access:https://doi.org/10.15252/emmm.202114073
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Summary:Abstract Natural killer (NK) cells provide a powerful weapon mediating immune defense against viral infections, tumor growth, and metastatic spread. NK cells demonstrate great potential for cancer immunotherapy; they can rapidly and directly kill cancer cells in the absence of MHC‐dependent antigen presentation and can initiate a robust immune response in the tumor microenvironment (TME). Nevertheless, current NK cell‐based immunotherapies have several drawbacks, such as the requirement for ex vivo expansion of modified NK cells, and low transduction efficiency. Furthermore, to date, no clinical trial has demonstrated a significant benefit for NK‐based therapies in patients with advanced solid tumors, mainly due to the suppressive TME. To overcome current obstacles in NK cell‐based immunotherapies, we describe here a non‐viral lipid nanoparticle‐based delivery system that encapsulates small interfering RNAs (siRNAs) to gene silence the key intrinsic inhibitory NK cell molecules, SHP‐1, Cbl‐b, and c‐Cbl. The nanoparticles (NPs) target NK cells in vivo, silence inhibitory checkpoint signaling molecules, and unleash NK cell activity to eliminate tumors. Thus, the novel NP‐based system developed here may serve as a powerful tool for future NK cell‐based therapeutic approaches.
ISSN:1757-4676
1757-4684

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