Temporal mapping of the anti-tumor effects of nanobody-based MSLN.CAR-T cell therapy in metastatic solid tumors.

ABSTRACT: Studies on the dynamic changes occurring in the tumor microenvironment (TME) following CAR-T cell therapy have been confounded by host lymphodepletion, multiple dosing and immunodeficient models. Here, a nanobody-based, mouse mesothelin-targeting CAR-T cell (A101) was developed, achieving effective primary tumor suppression, metastasis reduction, and improved survival after a single dose in immunocompetent, syngeneic mouse models without lymphodepletion. Temporal tumor profiling using RNA sequencing revealed initial downregulation of cell proliferation genes followed by upregulation of inflammation, epithelial-to-mesenchymal-transition (EMT) and extracellular matrix (ECM) modification genes in the CAR-T-treated tumors relative to mock-T-treated controls. This phenotype was reversed at a la

SUBMITTER: Stathopoulou C 

PROVIDER: S-EPMC12190766 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature