MMP3 overexpression enhances CAR-T cell infiltration and antitumor activity in a CAF-enriched solid tumor model.

ABSTRACT:

Background

Chimeric antigen receptor (CAR) T cell therapy has shown remarkable success in hematologic malignancies but faces substantial challenges in solid tumors. One of the main obstacles is the extracellular matrix (ECM), which serves as the physical barrier that hinders T cell infiltration into tumor tissues.

Methods

We engineered CAR-T cells targeting mesothelin or B7H3 to co-express matrix metalloproteinase-3 (MMP3). We evaluated the effects of MMP3 overexpression on CAR-T cell proliferation, activation, cytotoxicity, and tumor infiltration using both in vitro Matrigel-based assays and in vivo xenograft and syngeneic models enriched with cancer-associated fibroblasts (CAFs).

Results

MMP3 overexpression did not impair CAR-T cell proliferation, activation, or cyt

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC12853521 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature