CAR-engineered cytolytic Tregs reverse pulmonary fibrosis and remodel the fibrotic niche with limited CRS.

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a severe, diffuse, progressive, and fibrosing interstitial disease leading to respiratory failure and death in the absence of organ transplantation. Substantial evidence has confirmed the pivotal role of fibroblasts in the progression of IPF, yet effective therapeutic options are scarce. Single-cell transcriptomics profiling revealed that among the diverse fibroblast subsets, FAP1+ alveolar fibroblasts (AFs) were pivotal for the progression of IPF. On the basis of these findings, we developed FAP1-targeting chimeric antigen receptor cytotoxic effector regulatory T cells (CAR-cTregs), which leveraged the targeted killing advantage of the currently trending CAR-based immunotherapy for tumors and incorporated the immunosuppressive functions of Tregs to m

SUBMITTER: Jiang YH 

PROVIDER: S-EPMC12333945 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature