Ibrutinib and PD-1 Blockade Potentiate Mesothelin-Targeting CAR T-cell Therapy in Preclinical Models of Pancreatic Cancer.

ABSTRACT:

Purpose

Pancreatic ductal adenocarcinoma (PDAC) remains refractory to chimeric antigen receptor (CAR) T-cell therapies because of its immunosuppressive microenvironment and a dense extracellular matrix deposited by cancer-associated fibroblasts (CAF), which impair CAR T-cell infiltration. To address these barriers, we previously developed a dual-targeting CAR-TEAM platform in which mesothelin-specific CAR T cells secrete a fibroblast activation protein (FAP)-targeting T-cell engager antibody molecule (TEAM) to simultaneously kill tumor cells and CAF. In this study, we leveraged mesothelin-targeting CAR T cells and tested rational drug combinations and optimal delivery strategies to enhance therapeutic efficacy and guide potential combinations that could be incorporated into a clini

SUBMITTER: Armstrong A 

PROVIDER: S-EPMC12720996 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature