The MET receptor tyrosine kinase is mutated or amplified in ~6% of non-small cell lung cancers (NSCLC) and overexpressed in NSCLC. Here, we report a novel shark-derived single-domain variable new antigen receptor (VNAR) with high MET affinity for theranostic applications. Following immunization of a juvenile nurse shark (Ginglymostoma cirratum) with the extracellular domain of human MET, we identified a VNAR clone exhibiting high MET selectivity in vitro. As a bivalent human Fc fusion, vMET1-Fc was selectively internalized by MET-expressing cell lines and xenografts. Radiolabeled with zirconium-89 (89ZrZr-vMET1-Fc), it enabled PET/CT detection of MET-positive NSCLC xenografts. As a therapeutic, 177LuLu-vMET1-Fc delayed tumor growth in MET-mutant and MET-amplified cell line-derived xenografts. Non-human primate studies in healthy rhesus macaques confirmed favorable biodistribution, predictable clearance, and minimal off-target uptake. Together, these findings establish vMET1-Fc as a theranostic agent for imaging and treating MET-altered NSCLC.
LeBeau et al. (Mon,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: