Immunome Research
Open Access

Immuno-capture LC-MS/MS hybrid assay methodology in ADC bioanalysis

2^nd International Conference on Antibodies and Therapeutics

July 11-12, 2016 Philadelphia, USA

Ang Liu

Bristol-Myers Squibb, USA

Posters & Accepted Abstracts: Immunome Res

Abstract :

Antibody drug conjugates (ADCs) are complex molecules composed of two pharmacologically distinct components, the cytotoxic payload and the antibody. The measurement of the payload molecules that are attached to the antibody in vivo is important for the evaluation of the safety and efficacy of ADCs, and can also provide distinct information compared to the antibody-related analytes. However, analyzing the antibody-conjugated payload is challenging and in some cases may not be feasible. The in vivo change in drug antibody ratio (DAR), due to deconjugation, biotransformation or other clearance phenomena, generates unique and additional challenges for ADC analysis in biological samples. We will present a novel hybrid approach with immuno-capture of the ADC, payload cleavage by specific enzyme, and LC-MS/MS of the cleaved payload to quantitatively measure the concentration of payload molecules still attached to the antibody in plasma. The hybrid conjugated payload assay was fully validated and successfully applied to IND-enabling toxicology studies. In addition, the payload molecule could undergo metabolism without deconjugation from the antibody, which will potentially affect the potency of the ADC. The selectivity of MS/MS detection offers easy and simultaneous measurement of the potential metabolism. The success of this assay prompted us to establish comprehensive hybrid methodology for the measurement of total antibody and conjugated antibody in fully supporting ADC bioanalysis, which will also be discussed in the presentation.

Biography :

Email: Ang.Liu@bms.com