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MEDI3726

Development stage: Discontinued
Lead developer: AstraZeneca
Modality: Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Antibody Fragments → Engineered Antibody Formats → Antibody-Based Therapeutics
Administration: Intravenous

Overview

MEDI3726 is an antibody-drug conjugate (ADC) designed to target prostate-specific membrane antigen (PSMA), which is highly expressed in prostate cancer cells. It consists of a humanized monoclonal antibody (J591) engineered to bind PSMA and conjugated via a valine-alanine dipeptide linker to tesirine, a cytotoxic pyrrolobenzodiazepine (PBD) dimer that acts as a DNA minor groove crosslinking agent. Upon binding to PSMA on tumor cells and internalization, the PBD toxin is released inside the cell where it crosslinks DNA and induces cell death. The drug was developed by MedImmune and ADC Therapeutics (manufactured by AstraZeneca) for use in metastatic castration-resistant prostate cancer after progression on standard therapies such as abiraterone or enzalutamide and taxane-based chemotherapy. MEDI3726 was discontinued in development due to safety and efficacy issues.

Other names: anti-PSMA/PBD ADC MEDI3726

Targets

PSMA (Prostate-specific membrane antigen)

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