Biotransformation and stability of antibody-drug conjugates: Payload metabolism and linker cleavage delineation

Bioanalysis

Volumn 7, Issue 11, 2015, Pages 1319-1323

  Rangan, Vangipuram S ^a   Myler, Heather ^a   Kozhich, Alexander ^a   Wang, Jian ^a   Randazzo, Renee ^b   Deshpande, Shrikant ^a  

^a BRISTOL MYERS SQUIBB   (United States)

^b Global Manufacturing and Supply Biologics Development and Operations   (United States)

Author keywords

active antibody drug conjugates; bioanalytical assay; biotransformation; conjugated antibody; conjugated payload; drug to antibody ratio; linker cleavage; unconjugated payload

Indexed keywords

ANTIBODY CONJUGATE; CYTOTOXIC AGENT; DRUG;

DRUG BINDING; DRUG CONJUGATION; DRUG DESIGN; DRUG DISPOSITION; DRUG METABOLISM; DRUG SPECIFICITY; DRUG STABILITY; HUMAN; IMMUNOASSAY; LIQUID CHROMATOGRAPHY; NOTE; TANDEM MASS SPECTROMETRY; ANIMAL; BIOTRANSFORMATION; CHEMICAL ANALYSIS; CHEMISTRY; METABOLISM; PROCEDURES; PROTEIN STABILITY;

ANIMALS; BIOTRANSFORMATION; CHEMISTRY TECHNIQUES, ANALYTICAL; DRUG STABILITY; HUMANS; IMMUNOCONJUGATES; PHARMACEUTICAL PREPARATIONS; PROTEIN STABILITY;

EID: 84933518849     PISSN: 17576180     EISSN: 17576199     Source Type: Journal    
DOI: 10.4155/bio.15.50     Document Type: Note

References (6)

1. Chari RVJ. Targeted cancer therapy: conferring specificity to cytotoxic drugs. Acc. Chem. Res. 41 (1), 98-107 (2008).
2. Kaur S, Xu K, Saad OM, Dere RC, Carrasco-Triguero M. Bioanalytical assay strategies for the development of antibody drug conjugate biotherapeutics. Bioanalysis 5 (2), 201-226 (2013).
3. Gorovits B, Alley SC, Bilic S et al. Bioanalysis of antibodydrug conjugates: American Association of Pharmaceutical Scientists antibody-drug conjugate working group position paper. Bioanalysis 5 (9), 997-1006 (2013).
4. Nolting B. Linker technologies for antibody-drug conjugates. Methods Mol. Biol. 1045, 71-100 (2013).
5. Alley SC, Benjamin DR, Jeffrey SC et al. Contribution of linker stability to the activities of anticancer immunoconjugates. Bioconjug. Chem. 19 (3), 759-765 (2008).
6. Xu K, Liu L, Dere R et al. Characterization of the drug-to-antibody ratio distribution for antibody-drug conjugates in plasma/serum. Bioanalysis 5 (9), 1057-1071 (2013).