Mayo Clinic researchers found that drugs used for advanced thyroid cancer can restore markers on aggressive tumor cells, allowing CAR-T cell therapy to better identify and attack them.

Researchers at the Mayo Clinic have identified a strategy to improve CAR-T cell therapy for solid tumors by restoring specific markers on cancer cells. In a preclinical study published in Molecular Cancer, the team used drugs to increase the presence of the thyroid-stimulating hormone receptor (TSHR) on aggressive thyroid cancer cells. This process, known as redifferentiation, allowed engineered CAR-T cells to effectively target and control tumors that had previously escaped detection.

Overcoming Antigen Loss

CAR-T cell therapy works by engineering immune cells to recognize specific antigens on cancer cells. While successful in treating blood cancers, the therapy often struggles with solid tumors because these cancers can lose or reduce the antigens that CAR-T cells are designed to target. The Mayo Clinic team focused on TSHR, a protein typically found on thyroid cells, which is often absent in the most aggressive form of the disease, anaplastic thyroid cancer.

Combining Drugs and Immunotherapy

The researchers utilized MAPK pathway inhibitors, specifically the FDA-approved drugs trametinib and dabrafenib, to restore TSHR expression on tumor cells. In patient-derived models, this combination therapy resulted in superior tumor control and survival compared to using either treatment alone. The study indicated that the drugs did not hinder the CAR-T cells' ability to multiply or attack, and that two weeks of concurrent treatment was sufficient to improve therapeutic activity.