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Related Experiment Video

Updated: Jan 9, 2026

Computer-Aided Three-Dimensional Visualization in the Treatment of Locally Advanced Thyroid Cancer
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Computer-Aided Three-Dimensional Visualization in the Treatment of Locally Advanced Thyroid Cancer

Published on: June 9, 2023

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Optimized CART Cell Therapy for Metastatic Aggressive Thyroid Cancer.

Claudia Manriquez Roman, Elizabeth L Siegler, Justyna J Gleba

    Biorxiv : the Preprint Server for Biology
    |December 3, 2025
    PubMed
    Summary
    This summary is machine-generated.

    We developed thyroid-stimulating hormone receptor (TSHR)-targeted chimeric antigen receptor T (CART) cell therapy for thyroid cancer. Combining TSHR-CART cells with MAPK inhibitors enhances efficacy against aggressive, dedifferentiated tumors by restoring TSHR expression.

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    Area of Science:

    • Oncology
    • Immunotherapy
    • Molecular Biology

    Background:

    • Thyroid cancer mortality is linked to aggressive, metastatic tumors.
    • Chimeric antigen receptor T (CART) cell therapy shows promise but faces challenges like target downregulation.
    • Thyroid-stimulating hormone receptor (TSHR) is a target for differentiated thyroid cancers.

    Purpose of the Study:

    • To develop and evaluate a novel TSHR-targeted CART cell therapy for aggressive thyroid cancers.
    • To investigate combination strategies to overcome TSHR downregulation in dedifferentiated thyroid cancers.
    • To assess the efficacy of combining TSHR-CART cells with mitogen-activated protein kinase (MAPK) inhibitors.

    Main Methods:

    • Development of TSHR-targeted CART cells.
    • In vitro and in vivo testing against TSHR+ cell lines and patient-derived xenografts.
    • Combination therapy using TSHR-CART cells and MAPK inhibitors.

    Main Results:

    • TSHR-CART cells demonstrated antigen-specific activation and antitumor effects.
    • Dedifferentiated thyroid cancers showed TSHR downregulation.
    • Combination therapy significantly increased TSHR expression, enhanced antitumor efficacy, and prolonged survival in xenografts compared to monotherapy.

    Conclusions:

    • TSHR-CART cell therapy is a potential treatment for differentiated thyroid cancers.
    • MAPK inhibitors can restore TSHR expression in dedifferentiated thyroid cancers.
    • Combination therapy with TSHR-CART cells and MAPK inhibitors offers a potent strategy against aggressive thyroid cancers.