Li H, Zhou X, Wang G, et al. CAR-T Cells Targeting TSHR Demonstrate Safety and Potent Preclinical Activity Against Differentiated Thyroid Cancer. Journal of Clinical Endocrinology & Metabolism. 2021; (doi: 10.1210/clinem/dgab819).
Directing chimeric antigen receptor T cells (CAR T) to thyroid-stimulating hormone receptor (TSHR) might benefit some patients with differentiated thyroid cancer (DTC), researchers believe. To date, CAR T therapy for solid tumors has been held back by a lack of differentially expressed cell surface molecules that can be targeted without triggering safety issues. Scientists in China, however, have identified TSHR — which is highly expressed in 90.8% of papillary thyroid cancer, 89.2% of follicular thyroid cancer, on 78.2% of the cervical lymph node metastases, and 86.7% of radioiodine refractory (RAI-R) diseases — as a latent target antigen for T-cell therapy. The team developed three different anti-TSHR CAR Ts, all of which promote significant anti-tumor activity in vitro. However, only one of the three — the one developed from the monoclonal antibody K1-70 — also demonstrated therapeutic efficacy in vivo. Preclinical testing in a xenograft mouse model of DTC revealed no toxic effects associated with K1-70 CAR T. Based on the evidence, the study authors agreed that the approach has merit and should be explored further in clinical trials.