Title:Targeting TRIM29 As a Negative Regulator of CAR-NK Cell
Effector Function to Improve Antitumor Efficacy of these Cells:
A Perspective
Volume: 24
Issue: 4
Author(s): Zahra Saleh, Maryam Noroozi, Mahsa Eshkevar Vakili, Dieter Kabelitz, Hamid Nasrollahi and Kurosh Kalantar*
Affiliation:
- Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Autoimmune Disease Research Center, School of Medicine, Shiraz
University of Medical Sciences, Shiraz, Iran
- Center of Excellence for Clinical Immunology, School of
Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Keywords:
Tumor microenvironment, TRIM29, CAR-T cell, CAR-NK cell, chemotherapy, immunotherapy.
Abstract: Natural killer (NK) cells are among the most important cells in innate immune
defense. In contrast to T cells, the effector function of NK cells does not require prior
stimulation and is not MHC restricted. Therefore, chimeric antigen receptor (CAR)-NK
cells are superior to CAR-T cells. The complexity of the tumor microenvironment (TME)
makes it necessary to explore various pathways involved in NK cell negative regulation.
CAR-NK cell effector function can be improved by inhibiting the negative regulatory
mechanisms. In this respect, the E3 ubiquitin ligase tripartite motif containing 29
(TRIM29) is known to be involved in reducing NK cell cytotoxicity and cytokine
production. Also, targeting TRIM29 may enhance the antitumor efficacy of CAR-NK
cells. The present study discusses the negative effects of TRIM29 on NK cell activity
and proposes genomic deletion or suppression of the expression of TRIM29 as a novel
approach to optimize CAR-NK cell-based immunotherapy.
