Format

Send to

Choose Destination
Drug Metab Dispos. 2015 Sep;43(9):1341-4. doi: 10.1124/dmd.115.064253. Epub 2015 Jun 22.

Intracellular Catabolism of an Antibody Drug Conjugate with a Noncleavable Linker.

Author information

1
Department of Pharmacokinetics and Drug Metabolism (B.M.R., D.A.R., S.K.P.) and Therapeutic Innovation Unit (K.J.H., M.E.T., W.C.F.), Amgen, Inc., Seattle, Washington.
2
Department of Pharmacokinetics and Drug Metabolism (B.M.R., D.A.R., S.K.P.) and Therapeutic Innovation Unit (K.J.H., M.E.T., W.C.F.), Amgen, Inc., Seattle, Washington drock@amgen.com.

Abstract

Antibody drug conjugates are emerging as a powerful class of antitumor agents with efficacy across a range of cancers; therefore, understanding the disposition of this class of therapeutic is crucial. Reported here is a method of enriching a specific organelle (lysosome) to understand the catabolism of an anti-CD70 Ab-MCC-DM1, an antibody drug conjugate with a noncleavable linker. With such techniques a higher degree of concentration-activity relationship can be established for in vitro cell lines; this can aid in understanding the resultant catabolite concentrations necessary to exert activity.

PMID:
26101225
DOI:
10.1124/dmd.115.064253
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center