TSH Ligand-Based CAR-T Cell Effectively Eradicates TSHR-Positive Thyroid Cancer with Favorable Safety Profile.

ABSTRACT: CAR-T therapy faces significant challenges in solid tumors, including the shortage of targetable antigen and the immunogenicity of CAR molecules. Here, TSHR is identified as specifically expressed in DTC, but absent in other normal tissues, making it an ideal target for CAR-T therapy. To overcome CAR immunogenicity, a novel CAR molecule is engineered using TSH (TSH-CAR), the natural ligand of TSHR, as the antigen-binding domain to target TSHR. The TSH-CAR-T cells demonstrate effective antitumor activity against TSHR-positive differentiated thyroid cancer (DTC) cell lines in vitro, accompanied by cytokine release (IFNγ, IL-2) and robust proliferation. In addition, TSH-CAR-T cells achieved complete tumor eradication and sustained remission in two distinct thyroid cancer xenograft models. Fur

SUBMITTER: Wang F 

PROVIDER: S-EPMC12697831 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature