Zevontabart

Zevontabart (MYTX-011 Antibody; Q-397) is a pH-dependent anti- c-MET antibody. Zevontabart regulates the trafficking process of c-MET to reduce receptor recycling, and enhances its own endocytosis and accumulation in c-MET-expressing cells. Zevontabart induces cytotoxicity in solid tumor cells and exerts anti-tumor activity in a non-small cell lung cancer xenograft mouse model. Zevontabart can be used to synthesize ADC, such as: MYTX-011. Zevontabart can be used in studies related to non-small cell lung cancer, with its corresponding isotype control being Human IgG1 kappa, Isotype Control ^[1].

In Vivo, Zevontabart (0-6 mg/kg; i.v.; single administration) exhibits antitumor efficacy in NCI-H1975 NSCLC, NCI-H1373 NSCLC (with moderate c-MET expression), EBC-1 (with high c-MET expression), and NCI-H2122 NSCLC (with low c-MET expression) xenograft models^[1].

In Vitro, Zevontabart (50 nM; 120 s association, 300 s dissociation) binds to recombinant human c-MET in a pH-dependent manner, with a faster dissociation rate at the endolysosomal pH of 5.4 compared to the neutral pH of 7.4^[1]. Zevontabart (10 nM; 0.5-3 h) accumulates highly in lysosomes of NCI-H1975 c-MET+ non-small cell lung cancer (NSCLC) cells^[1]. Zevontabart (25 nM; 30 min) shows low colocalization with Rab4+ rapidly recycling endosomes in EBC-1 c-MET+ cancer cells^[1].

References:
[1]. Gera N, et al. MYTX-011: A pH-Dependent Anti-c-MET Antibody-Drug Conjugate Designed for Enhanced Payload Delivery to c-MET-Expressing Tumor Cells. Mol Cancer Ther. 2024;23(9):1282-1293.