CoupledCAR technology for treating thyroid cancer.

Abstract

e15027 Background: Significant challenges restrict CAR-T cell therapy to treat solid tumors. Methods: Here, we generated CAR-T cells using a novel CoupledCAR technology. Specifically, we engineered CoupledCAR T cells with lentiviral vectors encoding an anti-thyroid stimulating hormone receptor (TSHR) CAR molecule, and anti-TSHR CAR-T cells showed anti-tumor activities in vitro and in vivo experiments. Further, we treated refractory/relapsed post-thyroidectomy thyroid cancer patients using anti-TSHR CoupledCAR T cells, and observed the rapid expansion of CAR-T cells and the enhanced killing of tumor cells. Results: Both patients achieved PR (Partial Response). Patient Profile: Patient 1 Male, 64Y, Papillary Thyroid Carcinoma. In May 2017, thyroid cancer was diagnosed, bilateral total thyroidectomy, and right cervical lymph node functional dissection were performed in June, followed by iodine 131 isotope therapy. In December 2018, bilateral multiple cervical lymph nodes were enlarged. In February 2019, right neck lymphadenectomy was performed. Patient 2 Female, 60Y, Thyroid Carcinoma. In Aug 2013, a "double lobectomy of the thyroid gland” was performed. From Oct 2013 to Jan 2014, she received iodine 131 isotope therapy. In Sep 2014, she was diagnosed with iodine-resistant thyroid cancer. In 2016, 5 cycles of chemotherapy were performed. In Mar 2019, multiple metastases in both lungs and multiple enlarged lymph nodes were observed. Observations and Results: Patient 1: One month after infusion (M1), the patient was evaluated as PR: lymph node metastasis became undetectable and the size of the thoracic paratracheal tumor nodules decreased significantly. Three months after infusion (M3), the patient was evaluated as having a durable response, and the tumor tissue was substantially smaller than M1. Patient 2: M1, the patient was evaluated as PR (Partial Response): the tumor volume in the right lower lobe of the lung was reduced by approximately 67.51% (decreased from 65*55mm to 42*39mm). Three months after infusion (M3), compared with that before, the tumor volume was reduced by approximately 73.54% and SUV max value decreased from 14.9 to 2.8, therefore, the patient was evaluated as nCR (near complete remission). Conclusions: We show that TSHR is a good target for treating thyroid cancer, and our anti-TSHR CoupledCAR T cells are safe and effective for treating thyroid cancer. Recruitment is ongoing to evaluate the safety and efficacy of our CoupledCAR T cells. Further, since our CoupledCAR technology is a platform technology, we are developing it to treat other solid tumors using different target markers.