Derivation of AZD5335, a Novel FRα-Targeted TOP1i-Loaded ADC, for the Treatment of FRα-Expressing Cancers.

ABSTRACT:

Purpose

Folate receptor α (FRα) is expressed in most ovarian cancers. However, only patients with high expression levels are eligible for Elahere, an FRα-targeted microtubule inhibitor antibody-drug conjugate (ADC). Efficacy limitations and safety concerns underscore the need to develop next-generation FRα-targeted ADC to treat tumors expressing variable levels of FRα and incorporate different payloads to reduce safety risks. Herein, we present the characterization of AZD5335, a novel FRα-targeted topoisomerase-1 inhibitor ADC.

Experimental design

The efficacy of AZD5335 was assessed and correlated with FRα expression using cell- and patient-derived models. Focusing on models with low FRα, AZD5335 was directly compared with an Elahere analogue. Additionally, AZD5335 was eval

SUBMITTER: Zoeller JJ 

PROVIDER: S-EPMC12703359 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature