Tcf-1 protects anti-tumor TCR-engineered CD8⁺ T-cells from GzmB mediated self-destruction.

ABSTRACT:

Background

T-cell longevity is undermined by antigen-driven differentiation programs that render cells prone to attrition through several mechanisms. CD8 ⁺ T cells that express the Tcf-1 transcription factor have undergone limited differentiation and exhibit stem-cell-like replenishment functions that facilitate persistence. We engineered human CD8 ⁺ T cells to constitutively express Tcf-1 and a TCR specific for the NY-ESO-1 cancer-associated antigen. Co-engineered cells were assessed for their potential for adoptive cellular immunotherapy.

Methods

Tcf-1 mRNA encoding TCF-1B and TCF-1E isoforms, along with GzmB expression were assessed in CD62L ⁺ CD57 ^-, CD62L ^- CD57 ^-, and CD62L ^- CD57 ⁺ 

SUBMITTER: Zangari B 

PROVIDER: S-EPMC9588092 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature