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3H9-KGDEVD-monomethyl auristatin e
- Development stage
- Preclinical
- Lead developer
- Seoul National University
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
- Administration
- Intravenous
01
Overview
3H9-KGDEVD-monomethyl auristatin e is an antibody-drug conjugate (ADC) designed to target the prion-like glycoprotein PRND (Doppel), which is selectively expressed in tumor endothelial cells (TECs) and various cancer cells. The conjugate consists of a high-affinity anti-PRND monoclonal antibody (3H9) linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a specialized KGDEVD peptide linker. This linker is uniquely engineered for dual cleavage by both lysosomal cathepsin B and apoptotic caspases (caspase-3/7). This mechanism allows for initial drug release within target cells and subsequent feedback-driven release triggered by the apoptosis of neighboring cells, creating a potent bystander effect that helps overcome tumor antigen heterogeneity. Preclinical data suggests significant efficacy in hypervascular malignancies, including glioblastoma, sarcoma, and renal cell carcinoma, by disrupting tumor vasculature and inducing deep intratumoral penetration.
- Other names
- anti-PRND antibody-drug conjugate
02
Targets
CASP7 (Caspase-7)CTSB (Cathepsin B)CASP3 (Caspase-3)TUBB (Tubulin (alpha and beta subunits))
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