ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
TSH Ligand-Based CAR-T Cell Effectively Eradicates TSHR-Positive Thyroid Cancer with Favorable Safety Profile.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Proteogenomic characterization delineates clinically relevant subtypes of advanced differentiated thyroid cancer.Cell reports. Medicine · 2026Article
- Efficacy and safety of 125I seed implantation combined with thyroid-stimulating hormone suppression therapy in cervical lymph node metastases of differentiated thyroid carcinoma.Frontiers in endocrinology · 2026Article
- TSH Ligand-Based CAR-T Cell Effectively Eradicates TSHR-Positive Thyroid Cancer with Favorable Safety Profile.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
11 authors.
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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. Furthermore, for comprehensively evaluate the safety profile of TSH-CAR-T cell, a murine TSH-CAR (mTSH-CAR-T) is engineered, revealing that mTSH-CAR-T cells effectively control mTSHR-positive tumor growth without evident on-target/off-tumor effect in immunocompetent syngeneic mouse tumor models, except for the transient and reversible impairment of thyroid follicles, which is acceptable given prior thyroidectomy in DTC patients. The potent preclinical efficacy and favorable safety profile strongly support the clinical translation of TSH-CAR-T for patients suffering from metastatic and radioiodine-resistant DTC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.