Antibody Drug Conjugation (ADC)

Antibody–drug conjugate (ADC) is composed of a monoclonal antibody covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability of an antibody and highly potent killing effect of a small chemical to achieve accurate and efficient elimination of tumor cells.

There are two major categories of conjugation approaches. (1) Conjugation on ε-amino group via an active carboxylic acid ester; (2) Conjugation on reduced cysteine group via maleimide. An antibody protein can contain up to 90 lysine residues, of which 40 lysine residues are modifiable. Through the random coupling, varying numbers (0–8) of small-molecule toxins may be conjugated to an antibody, resulting in a wide drug-antibody ratio (DAR) distribution. Due to the limited number of cysteine sites, and therefore a DAR ratio of 1-4, conjugation on cysteine group can reduce the heterogeneity of ADC. However, opening the disulfide bond via reduction may alter the integrity of antibody protein.

BiCell Scientific’s ADC service includes two analytic chromatographs, using hydrophobic column and gel filtration column, which reveal the ADC effect on antibody aggregation and molecular size variation.