PD-1-CD28 fusion protein strengthens mesothelin-specific TRuC T cells in preclinical solid tumor models.

ABSTRACT:

Background

T cell receptor fusion constructs (TRuC) consist of an antibody-based single chain variable fragment (scFv) fused to a T cell receptor chain (TCR) and allow recognition of cancer cells in an HLA-independent manner. Unlike chimeric antigen receptors (CAR), TRuC are integrated into the TCR complex resulting in a functional chimera with novel specificity, whilst retaining TCR signaling. To further enhance anti-tumor function, we expressed a PD-1-CD28 fusion receptor in TRuC T cells aiming to prevent tumor-induced immune suppression and T cell anergy.

Methods

The activation level of engineered T cells was investigated in co-culture experiments with tumor cells followed by quantification of released cytokines using ELISA. To study T cell-mediated tumor cell lysis in vi

SUBMITTER: Lesch S 

PROVIDER: S-EPMC9947055 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature