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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Excoffier, Mélissa Janin-Bussat, Marie-Claire Beau-Larvor, Charlotte Troncy, Lysiane Corvaia, Nathalie Beck, Alain Klinguer-Hamour, Christine |
| Description | Country affiliation: France Author Affiliation: Excoffier M ( Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon IIIBP 60497, 74164 Saint-Julien-en-Genevois, France.); Janin-Bussat MC ( Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon IIIBP 60497, 74164 Saint-Julien-en-Genevois, France.); Beau-Larvor C ( Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon IIIBP 60497, 74164 Saint-Julien-en-Genevois, France.); Troncy L ( Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon IIIBP 60497, 74164 Saint-Julien-en-Genevois, France.); Corvaia N ( Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon IIIBP 60497, 74164 Saint-Julien-en-Genevois, France.); Beck A ( Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon IIIBP 60497, 74164 Saint-Julien-en-Genevois, France. Electronic address: alain.beck@pierre-fabre.com.); Klinguer-Hamour C ( Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon IIIBP 60497, 74164 Saint-Julien-en-Genevois, France. Electronic address: christine.klinguer.hamour@pierre-fabre.com.) |
| Abstract | Antibody-drug conjugates (ADCs) are becoming a major class of oncology therapeutics. They combine monoclonal antibody specificity for over-expressed tumor antigens and the high cytoxicity of small molecular drugs (SMDs) and can therefore selectively kill tumor cells while minimizing toxicity to normal cells. Nevertheless, the premature deconjugation of ADCs in the circulation may trigger off target toxicity in patients. The released free drug level must be low in circulation for an extended period of time as well as the de-conjugation rate to ensure an acceptable therapeutic window. As a result, the assessment of the stability of the linker between payload and mAb in the systemic circulation is of paramount importance before entering in clinical trial. Here we report a new universal method to immunocapture and analyze by LC-MS the stability and distribution of ADCs in sera from relevant preclinical species (mouse, rat and cynomolgus monkey). Furthermore we demonstrated that this workflow can be applied to both ADCs with cleavable and non cleavable linkers. Last but not least, the results obtained in cynomolgus serum using immunoprecipitation and LC-MS analysis were cross validated using an ELISA orthogonal method. As the ligand used for immunoprecipitation is targeting the Fc part of mAb (CaptureSelect™ Human IgG-Fc PK Biotin), this protocol can be applied to analyze the stability of virtually all ADCs in sera for preclinical studies without the need to prepare specific molecular tools. |
| File Format | HTM / HTML |
| ISSN | 15700232 |
| Journal | Journal of Chromatography B |
| Volume Number | 1032 |
| e-ISSN | 1873376X |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2016-10-01 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Analytical Chemistry Clinical Biochemistry Biochemistry |
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