Open AccessModulation of intrinsic inhibitory checkpoints using nano‐carriers to unleash NK cell activity
Author(s) -
Biber Guy,
Sabag Batel,
Raiff Anat,
BenShmuel Aviad,
Puthenveetil Abhishek,
Benichou Jennifer I C,
Jubany Tammir,
Levy Moria,
Killner Shiran,
BardaSaad Mira
Publication year - 2021
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202114073
Subject(s) - cancer immunotherapy , immune system , immunotherapy , tumor microenvironment , biology , cancer cell , microbiology and biotechnology , cancer research , immunology , cancer , genetics
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.