NR4A ablation improves mitochondrial fitness for long persistence in human CAR-T cells against solid tumors.

ABSTRACT:

Background

Antitumor effect of chimeric antigen receptor (CAR)-T cells against solid tumors is limited due to various factors, such as low infiltration rate, poor expansion capacity, and exhaustion of T cells within the tumor. NR4A transcription factors have been shown to play important roles in T-cell exhaustion in mice. However, the precise contribution of each NR4a factor to human T-cell differentiation remains to be clarified.

Methods

In this study, we deleted NR4A family factors, NR4A1, NR4A2, and NR4A3, in human CAR-T cells recognizing human epidermal growth factor receptor type 2 (HER2) by using the CRISPR/Cas9 system. We induced T-cell exhaustion in these cells in vitro through repeated co-culturing of CAR-T cells with Her2⁺A549 lung adenocar

SUBMITTER: Nakagawara K 

PROVIDER: S-EPMC11331892 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature