TUB-040, a Homogeneous and Hydrophilic NaPi2b-Targeting ADC with Stably Linked Exatecan, Exhibits Long-lasting Antitumor Activity and a Well-Tolerated Safety Profile.

ABSTRACT: TUB-040 is a highly homogeneous and hydrophilic antibody-drug conjugate (ADC) targeting sodium-dependent phosphate transport protein 2b (NaPi2b), a surface receptor overexpressed in ovarian cancer and non-small cell lung adenocarcinoma. Previous NaPi2b-directed therapies have shown target-mediated and expression-dependent clinical activity. However, none of the previous tubulin inhibitor-based ADCs have been able to leverage the full therapeutic potential of the target. TUB-040 was constructed with a drug-to-antibody ratio of 8 using the Tubutecan linker-payload technology based on ethynylphosphonamidates (P5 conjugation chemistry), a protease cleavage site, and exatecan, a potent topoisomerase 1 inhibitor. TUB-040 induces potent antigen-specific cytotoxicity against NaPi2b-expressing canc

SUBMITTER: Vogl AM 

PROVIDER: S-EPMC12580765 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature