Effect of chimeric antigen receptor T cells against protease-activated receptor 1 for treating pancreatic cancer.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with a 5-year survival rate of 6% following a diagnosis, and novel therapeutic modalities are needed. Protease-activated receptor 1 (PAR1) is abundantly overexpressed by both tumor cells and multiple stroma cell subsets in the tumor microenvironment (TME), thereby offering a suitable immunotherapy target.

Methods

A chimeric antigen receptor (CAR) strategy was applied to target PAR1 using a human anti-PAR1 scFv antibody fused to the transmembrane region with two co-stimulatory intracellular signaling domains of cluster of differentiation 28 (CD28) and CD137 (4-1BB), added to CD3ζ in tandem.

Results

The engineered PAR1CAR-T cells eliminated PAR1 overexpression and transforming growth factor (

SUBMITTER: Hung HC 

PROVIDER: S-EPMC10478223 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature