Back to Search
Start Over
Multi-step high-throughput conjugation platform for the development of antibody-drug conjugates.
- Source :
-
Journal of biotechnology [J Biotechnol] 2018 Jul 20; Vol. 278, pp. 48-55. Date of Electronic Publication: 2018 May 04. - Publication Year :
- 2018
-
Abstract
- Antibody-drug conjugates (ADCs) form a rapidly growing class of biopharmaceuticals which attracts a lot of attention throughout the industry due to its high potential for cancer therapy. They combine the specificity of a monoclonal antibody (mAb) and the cell-killing capacity of highly cytotoxic small molecule drugs. Site-specific conjugation approaches involve a multi-step process for covalent linkage of antibody and drug via a linker. Despite the range of parameters that have to be investigated, high-throughput methods are scarcely used so far in ADC development. In this work an automated high-throughput platform for a site-specific multi-step conjugation process on a liquid-handling station is presented by use of a model conjugation system. A high-throughput solid-phase buffer exchange was successfully incorporated for reagent removal by utilization of a batch cation exchange step. To ensure accurate screening of conjugation parameters, an intermediate UV/Vis-based concentration determination was established including feedback to the process. For conjugate characterization, a high-throughput compatible reversed-phase chromatography method with a runtime of 7 min and no sample preparation was developed. Two case studies illustrate the efficient use for mapping the operating space of a conjugation process. Due to the degree of automation and parallelization, the platform is capable of significantly reducing process development efforts and material demands and shorten development timelines for antibody-drug conjugates.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- Automation, Laboratory
Cation Exchange Resins
Chromatography, Reverse-Phase
Cysteine chemistry
Cysteine metabolism
Models, Chemical
Antibodies, Monoclonal analysis
Antibodies, Monoclonal chemistry
Antibodies, Monoclonal isolation & purification
Antibodies, Monoclonal metabolism
High-Throughput Screening Assays methods
Immunoconjugates analysis
Immunoconjugates chemistry
Immunoconjugates isolation & purification
Immunoconjugates metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4863
- Volume :
- 278
- Database :
- MEDLINE
- Journal :
- Journal of biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 29733878
- Full Text :
- https://doi.org/10.1016/j.jbiotec.2018.05.004