Targeting TRIM29 As a Negative Regulator of CAR-NK Cell
Effector Function to Improve Antitumor Efficacy of these Cells:
A Perspective

Zahra      Saleh; Maryam      Noroozi; Mahsa      Eshkevar Vakili; Dieter      Kabelitz; Hamid      Nasrollahi; Kurosh      Kalantar

doi:10.2174/1566524023666230510101525

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.

Keywords: Tumor microenvironment, TRIM29, CAR-T cell, CAR-NK cell, chemotherapy, immunotherapy.

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DOI https://dx.doi.org/10.2174/1566524023666230510101525	Print ISSN 1566-5240
Publisher Name Bentham Science Publisher	Online ISSN 1875-5666

Current Molecular Medicine

Targeting TRIM29 As a Negative Regulator of CAR-NK Cell Effector Function to Improve Antitumor Efficacy of these Cells: A Perspective

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