Engineering second-generation TCR-T cells by site-specific integration of TRAF-binding motifs into the CD247 locus.

ABSTRACT:

Background

The incorporation of co-stimulatory signaling domains into second-generation chimeric antigen receptors (CARs) significantly enhances the proliferation and persistence of CAR-T cells in vivo, leading to successful clinical outcomes.

Methods

To achieve such functional enhancement in transgenic T-cell receptor-engineered T-cell (TCR-T) therapy, we designed a second-generation TCR-T cell in which CD3ζ genes modified to contain the intracellular domain (ICD) of the 4-1BB receptor were selectively inserted into the CD247 locus.

Results

This modification enabled the simultaneous recruitment of key adaptor molecules for signals 1 and 2 on TCR engagement. However, the addition of full-length 4-1BB ICD unexpectedly impaired the expression and signaling of TCR

SUBMITTER: Lah S 

PROVIDER: S-EPMC10083865 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature