title: Intracellular Catabolism of an Antibody Drug Conjugate with a Noncleavable Linker.
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.
authors.affiliation: 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.
authors.forename: Brooke M
authors.initials: BM
authors.lastname: Rock
authors.affiliation: 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.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Tometsko
authors.affiliation: 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.
authors.forename: Sonal K
authors.initials: SK
authors.lastname: Patel
authors.affiliation: 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.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Hamblett
authors.affiliation: 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.
authors.forename: William C
authors.initials: WC
authors.lastname: Fanslow
authors.affiliation: 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.
authors.forename: Dan A
authors.initials: DA
authors.lastname: Rock
mesh_terms: D053282:CD27 Ligand / Q000276:immunology; D045744:Cell Line, Tumor; D006801:Humans; D018796:Immunoconjugates / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*
chemical_list: D053282:CD27 Ligand; D018796:Immunoconjugates; D004364:Pharmaceutical Preparations