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1A3-monomethyl auristatin E
- Development stage
- Preclinical
- Lead developer
- The University of Tokyo
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
- Administration
- Intravenous
01
Overview
1A3-monomethyl auristatin E is an experimental antibody-drug conjugate (ADC) designed to target Amphiregulin (AREG), a ligand for the Epidermal Growth Factor Receptor (EGFR) that is frequently overexpressed in breast cancer and other malignancies. The ADC consists of the monoclonal antibody 1A3, which specifically recognizes the C-terminal transmembrane stalk of AREG that remains on the cell surface after its extracellular domain is proteolytically cleaved by TACE/ADAM17. Upon binding to this stalk, the ADC is rapidly internalized, delivering the cytotoxic payload monomethyl auristatin E (MMAE) into the cell. MMAE is a potent antimitotic agent that inhibits tubulin polymerization, leading to cell cycle arrest at the G2/M phase and subsequent apoptosis. This therapeutic strategy leverages the specific internalization of the AREG stalk to selectively eliminate cancer cells while minimizing off-target toxicity.
- Other names
- Anti-AREG ADC1A3-vcMMAE
02
Targets
AREG neo-epitope (Cleaved amphiregulin transmembrane stalk neo-epitope)
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