(The platform has authorized to do further research and development in the affiliated company, T-E Meds, Inc.)
T-E Meds website: https://www.temeds.com/
The cytotoxic drug bundles are conjugated to antibody molecules to form ADCs. In our preferred constructs, the Fab part of the antibody molecule is reconfigured to single-chain variable fragment (scFv), so that the antibody molecule is presented as two “extended heavy chains” covalently associated by interchain disulfide bonds. For each heavy chain, the N-terminal is scFv, the center part is CH2-CH3 domains of immunoglobulin g1 chain, and at the C-terminal is a short peptide linker. The complexing of Zn2+ with the cysteine residue and the adjacent amino acids enhances the SH group as a nucleophile.
The conjugation of the cytotoxic drug bundles is thus made via a site-specific SH-maleimide "Michael Reaction" to the cysteine residues at the C-termini of the heavy chains. Two drug bundles are conjugated per antibody molecule. The ADC product is homogeneous with a finite DAR of 6, 8, or 10, using drug bundles carrying 3, 4, or 5 cytotoxic drug molecules.
An emerging consensus in the ADC field is that if an antibody drug conjugate maintains soluble and stable, higher DAR is more efficacious.
Here shows the preparation process of an ADC.
