Generation of Antibody Drug Conjugate (ADC) technologies for site specific conjugation to toxins

Antibody-Drug Conjugates (ADCs) are a targeted treatment technology for delivery of toxins
directly to cancer cells and a fast-growing class of oncology therapeutics, with eight ADCs
approved for clinical use. Most clinically-available ADCs are produced through either a
chemical reaction of lysine e-amino groups which produces heterogeneous products, or
conjugation through cysteine sulfhydryl groups activated by reducing the interchain disulfide
bonds, which may compromise antibody stability. We will introduce site-specific cysteine
mutations on antibodies for site-specific conjugation with toxic drugs. We will compare
different mutant antibodies as ADCs in functional models, to identify optimal stability,
function and efficacy characteristics.