Objective:

To investigate whether MAPK inhibitors can enhance the susceptibility of thyroid tumors to CAR T-cell therapy by restoring TSHR expression.

Approach:

• Study Design: Preclinical study using thyroid cancer models to assess the effects of MAPK inhibitors on TSHR expression and CAR T-cell efficacy.
• Treatment Methods: Utilized MEK inhibitor trametinib and BRAF inhibitor dabrafenib to induce redifferentiation and restore TSHR expression in anaplastic thyroid cancer models.
• Combination Therapy: Evaluated the effects of concurrent treatment with MAPK inhibitors and TSHR-directed CAR T cells on tumor control and survival.

Key Findings:

• MAPK inhibitors increased TSHR expression in aggressive thyroid cancer models.
• Concurrent treatment with MAPK inhibitors and TSHR-directed CAR T cells improved tumor control and survival compared to either treatment alone.
• Antigen density influenced the response of CAR T-cell therapy, with higher TSHR expression correlating with better outcomes.

Limitations:

• TSHR expression decreased rapidly after stopping MAPK inhibitors, indicating the need for further investigation into treatment timing.
• The study is preclinical and requires validation in clinical trials.

Sources:

• Mayo Clinic Press Release