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• W2803068495 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." @default.
• W2803068495 created "2018-05-17" @default.
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• W2803068495 date "2018-07-01" @default.
• W2803068495 modified "2023-10-18" @default.
• W2803068495 title "Multi-step high-throughput conjugation platform for the development of antibody-drug conjugates" @default.
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• W2803068495 doi "https://doi.org/10.1016/j.jbiotec.2018.05.004" @default.
• W2803068495 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29733878" @default.
• W2803068495 hasPublicationYear "2018" @default.
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