Bioanalysis of Antibody–Drug Conjugates: American Association of Pharmaceutical Scientists Antibody–Drug Conjugate Working Group Position Paper
- 3 May 2013
- journal article
- Published by Informa UK Limited in Bioanalysis
- Vol. 5 (9), 997-1006
- https://doi.org/10.4155/bio.13.38
Abstract
Antibody-drug conjugates (ADCs) typically consist of a cytotoxic drug covalently bound to an antibody by a linker. These conjugates have the potential to substantially improve efficacy and reduce toxicity compared with cytotoxic small-molecule drugs. Since ADCs are generally complex heterogeneous mixtures of multiple species, these novel therapeutic products present unique bioanalytical challenges. The growing number of ADCs being developed across the industry suggests the need for alignment of the bioanalytical methods or approaches used to assess the multiple species and facilitate consistent interpretation of the bioanalytical data. With limited clinical data, the current strategies that can be used to provide insight into the relationship between the multiple species and the observed clinical safety and efficacy are still evolving. Considerations of the bioanalytical strategies for ADCs based on the current industry practices that take into account the complexity and heterogeneity of ADCs are discussed.Keywords
This publication has 29 references indexed in Scilit:
- Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugatesNature Biotechnology, 2012
- Tunable Degradation of Maleimide–Thiol Adducts in Reducing EnvironmentsBioconjugate Chemistry, 2011
- The Pharmacologic Basis for Antibody-Auristatin Conjugate ActivityJournal of Pharmacology and Experimental Therapeutics, 2009
- Therapeutic antibodies: successes, limitations and hopes for the futureBritish Journal of Pharmacology, 2009
- Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology productsJournal of Pharmaceutical and Biomedical Analysis, 2008
- Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic indexNature Biotechnology, 2008
- Anti-CD22-MCC-DM1 and MC-MMAF Conjugates: Impact of Assay Format on Pharmacokinetic Parameters DeterminationBioconjugate Chemistry, 2008
- Structural characterization of the maytansinoid–monoclonal antibody immunoconjugate, huN901–DM1, by mass spectrometryProtein Science, 2005
- Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignanciesBlood, 2004
- Pharmacokinetics and Biodistribution of the Antitumor Immunoconjugate, Cantuzumab Mertansine (huC242-DM1), and Its Two Components in MiceJournal of Pharmacology and Experimental Therapeutics, 2003