Immuno-PET Detects Antibody-Drug Potency on Coadministration with Statins.

ABSTRACT: The human epidermal growth factor receptor 2 (HER2)-targeting trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) are antibody-drug conjugates (ADC) clinically used to treat HER2-positive breast cancer, with the latter receiving clinical approval in 2021 for HER2-positive gastric cancer. Lovastatin, a cholesterol-lowering drug, temporally elevates cell-surface HER2 in ways that enhance HER2-ADC binding and internalization. Methods: In an NCIN87 gastric xenograft model and a gastric patient-derived xenograft model, we used the ⁸⁹Zr-labeled or ⁶⁴Cu-labeled anti-HER2 antibody trastuzumab to investigate the dosing regimen of ADC therapy with and without coadministration of lovastatin. We compared the ADC efficacy of a multiple-dose ADC regime, which re

SUBMITTER: Brown EL 

PROVIDER: S-EPMC10586480 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature