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1959-sss + DM4
- Development stage
- Preclinical
- Lead developer
- MediaPharma
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
- Administration
- Intravenous
01
Overview
1959-sss + DM4 is a site-specific, linker-less antibody-drug conjugate (ADC) designed to target Galectin-3-binding protein (LGALS3BP/Gal-3BP), a glycoprotein overexpressed in various solid tumors. The ADC utilizes a humanized monoclonal antibody (1959) engineered with three cysteine substitutions (S220C, S226C, S229C, denoted as 'sss') to facilitate the direct, site-specific attachment of the cytotoxic payload DM4 (ravtansine) via disulfide bonds. Unlike most ADCs that require cellular internalization and lysosomal degradation for payload release, 1959-sss + DM4 is a non-internalizing ADC that exploits the high reducing potential of the tumor microenvironment to trigger the extracellular release of DM4. Once released, DM4 binds to tubulin and inhibits microtubule polymerization, leading to cell cycle arrest and apoptosis. This drug has shown potent preclinical activity in models of melanoma, neuroblastoma, glioblastoma, adenoid cystic carcinoma, and bladder cancer.
- Other names
- anti-LGALS3BP ADCanti-LGALS-3BP ADCanti-LGALS 3BP ADCanti-Gal-3BP ADCanti-Gal3BP ADCanti-Gal 3BP ADC
02
Targets
TUBB (Tubulin (alpha and beta subunits))LGALS3BP (Galectin-3-binding protein)
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