Immunotherapies and CAR T cell therapies in thyroid carcinoma mouse models

Abstract

Anaplastic thyroid cancer (ATC) is a rare but highly aggressive solid tumour entity with limited treatment options. Hence, there is a necessity for a novel efficient therapeutic approach. In this thesis, ROR1 was validated as a promising CAR T cell target for ATC, due to its high RNA and protein expression in ATC and low to no expression in healthy adult tissues. ROR1-targeting CAR T cells efficiently and specifically lysed ROR1-expressing ATC cell lines in vitro, in 2D and 3D models. In vivo, CAR T cell monotherapy inhibited small tumours and metastasis, but failed to hinder the established tumour growth. This issue was addressed by combining CAR T cells with a multikinase inhibitor lenvatinib, which led to decreased established tumour development, enhanced CAR T cell efficiency, and inhibition of the immunosuppressive subtype of cancer-associated fibroblasts. In summary, the combination of ROR1-CAR T cells and lenvatinib was identified as a promising therapeutic approach in ATC.