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Updated: Feb 13, 2026

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Una teranóstica de anticuerpo de tiburón (VNAR) dirigida a MET para el cáncer de pulmón no microcítico

Rachel L Minne, Jayden L West, Natalie Y Luo

bioRxiv : the preprint server for biology

|February 12, 2026

Abstract:

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 ([ ⁸⁹ Zr]Zr-vMET1-Fc), it enabled PET/CT detection of MET-positive NSCLC xenografts. As a therapeutic, [ ¹⁷⁷ Lu]Lu-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.

One Sentence Summary:

A shark-derived antibody selectively targeting MET shows preclinical efficacy as a theranostic agent for MET-altered cancers.

Palabras clave:

anticuerpo de tiburón VNAR MET teranóstica cáncer de pulmón no microcítico imagenología terapia

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