Antibody drug conjugates (ADCs) are an emerging class of drugs that are used primarily in the treatment of cancer. These unique therapeutics are comprised of three main components: an antibody, a drug payload, and a linker. The antibody component acts to direct the delivery of the payload, which is transported and subsequently released in proximity to its intended target. As these therapeutics have progressed from preclinical candidates into human clinical trials, efforts have been focused on developing processes for manufacturing ADCs and toward developing fundamental understanding of these complex systems. This presentation will review process development and scale up efforts for a random conjugation process involving initial functionalization of lysine residues with 2-iminothiolane, followed by conjugation with a maleimide containing payload-linker construct. Process development highlights to be discussed include efforts to understand the  stability and reactivity of the thiolated antibody intermediate, the impact of key process parameters on thiolation performance, and the impact of cyclized 2-iminothiolane residues on ADC stability.

Antibody drug conjugates: Process development and analytical considerations

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.