Monitoring of antibody-drug conjugation reactions with UV/Vis spectroscopy
| Autor: | Michaela Wendeler, Jonas Rogalla, Matthias Rüdt, Sebastian Andris, Jürgen Hubbuch |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Immunoconjugates 010405 organic chemistry Chemistry Antibodies Monoclonal Bioengineering General Medicine 01 natural sciences Applied Microbiology and Biotechnology Combinatorial chemistry 0104 chemical sciences Maleimides 03 medical and health sciences 030104 developmental biology Ultraviolet visible spectroscopy Coumarins Drug conjugation Immunoglobulin G Partial least squares regression Spectrophotometry Ultraviolet Biotechnology Conjugate |
| Zdroj: | Journal of Biotechnology. 288:15-22 |
| ISSN: | 0168-1656 |
| Popis: | The conjugation reaction of monoclonal antibodies (mAbs) with small-molecule drugs is a central step during production of antibody-drug conjugates (ADCs). The ability to monitor this step in real time can be advantageous for process understanding and control. Here, we propose a method based on UV/Vis spectroscopy in conjunction with partial least squares (PLS) regression for non-invasive monitoring of conjugation reactions. In experiments, the method was applied to conjugation reactions with two surrogate drugs in microplate format as well as at 20 ml scale. All calibrated PLS models performed well in cross-validation ( Q 2 > 0.975 for all models). In microplate format, the PLS models were furthermore successfully validated with an independent prediction set ( R p r e d 2 = 0.9770 resp. 0.8940). In summary, the proposed method provides a quick and easily implementable tool for reaction monitoring of ADC conjugation reactions and may in the future support the implementation of Process Analytical Technologies (PAT). |
| Databáze: | OpenAIRE |
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