Identification of antibody-drug conjugate payloads which are substrates of ATP-binding cassette drug efflux transporters.

ABSTRACT:

Aim

Antibody-drug conjugates (ADCs) feature an antibody recognizing a specific protein joined to a potent toxic payload. Numerous antibody-drug conjugates have received FDA approval; however, clinical resistance arises. Resistance mechanisms include decreased expression or mutation of the antibody target, impaired payload release, or increased expression of ATP-binding cassette (ABC) efflux transporters associated with multidrug resistance. We therefore sought to characterize the interactions of ABC multidrug transporters with ADC payloads.

Methods

We performed a high-throughput screen with 27 common ADC payloads using cells lines expressing ABC transporters P-glycoprotein (P-gp, encoded by ABCB1) or ABCG2 (encoded by ABCG2). Confirmatory assays were also perfo

SUBMITTER: Roth JS 

PROVIDER: S-EPMC12154920 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature