Scientific Associate Director BMS Short Hills, New Jersey
Antibody drug conjugates (ADCs) that combine potent payload cytotoxicity and target specificity represent a significant advancement in cancer therapy. The structural complexity of ADCs poses unique bioanalytical challenges compared to small molecule or therapeutic protein assays. To characterize the PK properties of each ADC, three distinct bioanalytical assays are needed: free payload, total conjugated payload and total antibody with each presenting its unique challenges: 1) very low detection limit and minimum ADC conversion to cytotoxin for the free payload assay; 2) high recovery of ADC during immunocapture, consistent enzymatic digestion and quantitation of released payload for the conjugated payload assay; 3) specific capture of total antibody with minimum nonspecific interference for traditional ELISA or MSD based assay. In this poster, all three required assays were developed and validated using (hybrid) LC-MS/MS based techniques that overcame the above mentioned challenges to support a FIH study for a new generation therapeutic ADC
Learning Objectives:
Deeper understanding of the diverse linker chemistry/payloads
learn the best work practices needed for developing these high-quality ADC assays.
Obtain pratical knowlege of how to support ADC FIH clincal study using all LCMSMS based assays.
