MET is a widely overexpressed critical oncogene ineffectively targeted by multiple large pharmaceutical companies. Taking advantage of the biochemically favorable properties of nanobodies, we developed a novel chimeric antigen receptor (CAR) targeting MET. Our MET CAR demonstrates low tonic signaling, high polyfunctional cytokine production, improved killing, T cell avidity and in vivo efficacy in a triple negative breast cancer model metastatic to lung. With Blavatnik funding we will (1) develop a humanized version, (2) optimize lipid nanoparticle encapsulation and T cell-targeted delivery for in vivo dosing, and (3) establish efficacy in a humanized PDX model in vivo.