Challenges and new frontiers in analytical characterization of antibody-drug conjugates

MAbs
Anil WaghTapan K Das

Abstract

Antibody-drug conjugates (ADCs) are a growing class of biotherapeutics in which a potent small molecule is linked to an antibody. ADCs are highly complex and structurally heterogeneous, typically containing numerous product-related species. One of the most impactful steps in ADC development is the identification of critical quality attributes to determine product characteristics that may affect safety and efficacy. However, due to the additional complexity of ADCs relative to the parent antibodies, establishing a solid understanding of the major quality attributes and determining their criticality are a major undertaking in ADC development. Here, we review the development challenges, especially for reliable detection of quality attributes, citing literature and new data from our laboratories, highlight recent improvements in major analytical techniques for ADC characterization and control, and discuss newer techniques, such as two-dimensional liquid chromatography, that have potential to be included in analytical control strategies.

References

Feb 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·G W SeeganV N Schumaker
Mar 23, 2002·Protein Science : a Publication of the Protein Society·Ronald L WoodburyLinda L Randall
Jun 5, 2003·Nature Biotechnology·Svetlana O DoroninaPeter D Senter
Oct 27, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kevin J HamblettJoseph A Francisco
Feb 22, 2005·Methods : a Companion to Methods in Enzymology·Claire Delahunty, John R Yates
Jun 10, 2005·Rapid Communications in Mass Spectrometry : RCM·Alexandru C LazarWei Zhang
Aug 6, 2005·Protein Science : a Publication of the Protein Society·Lintao WangWei Zhang
Apr 29, 2006·Protein Engineering, Design & Selection : PEDS·Charlotte F McDonaghPaul Carter
Aug 21, 2007·Accounts of Chemical Research·Ravi V J Chari
Mar 5, 2008·Bioconjugate Chemistry·Stephen C AlleyPeter D Senter
Jul 22, 2008·Nature Biotechnology·Jagath R JunutulaWilliam Mallet
Sep 23, 2009·Bioconjugate Chemistry·Laurent Ducry, Bernhard Stump
Apr 14, 2011·MAbs·Josef Vlasak, Roxana Ionescu
Aug 18, 2012·Journal of Chromatography. a·W Hampton Henley, James W Jorgenson
Sep 4, 2012·Expert Opinion on Biological Therapy·Barbara Pro, Guilherme Fleury Perini
Sep 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jun Y AxupPeter G Schultz
Dec 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Paresh AgarwalCarolyn R Bertozzi
Mar 29, 2013·Nature Reviews. Drug Discovery·Rachel S ZolotRyan P Million
May 1, 2013·Nature Reviews. Drug Discovery·Asher Mullard
Jun 20, 2013·Bioconjugate Chemistry·Nicholas J BoylanJennifer S Laurence
Aug 6, 2013·Methods in Molecular Biology·Ingrid Sassoon, Véronique Blanc
Aug 6, 2013·Methods in Molecular Biology·Yan Chen
Aug 6, 2013·Methods in Molecular Biology·Joyce Lin, Alexandru C Lazar
Oct 19, 2013·MAbs·Christopher R Behrens, Bin Liu
Dec 24, 2013·Bioconjugate Chemistry·Santiago E FariasArvind Rajpal
Jan 21, 2014·Proceedings of the National Academy of Sciences of the United States of America·Feng TianPuja Sapra
Feb 25, 2014·Bioconjugate Chemistry·Yilma T AdemOsigwe Esue
May 29, 2014·Expert Opinion on Biological Therapy·Felicitas Thol, Richard F Schlenk

❮ Previous
Next ❯

Citations

Jan 16, 2020·Antibodies·Donmienne LeungYiqing Feng
Feb 20, 2021·Expert Opinion on Biological Therapy·Martin De CeccoLisa L McDermott
Sep 1, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Han Young KimJu Hee Ryu
May 28, 2019·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Antony LechnerYannis-Nicolas François
May 9, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sandeep Surendra PanikarPedro Salas
Jul 10, 2021·Angewandte Chemie·Shipeng HeChunquan Sheng
Jan 1, 2021·Journal of Medicinal Chemistry·Mona AlasKamaljit Kaur
Sep 3, 2021·Journal of Separation Science·Yutaka Matsuda

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis
reversed-phase
size-exclusion chromatography
ion exchange chromatography
thermal stress
differential scanning calorimetry

Software Mentioned

iCIEF
Flowcam

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.