| Added by | mollevi |
|---|---|
| Last modified by | alainmange |
| Group name | PlateformePP2I |
| Item Type | Journal Article |
| Title | Increment in Drug Loading on an Antibody-Drug Conjugate Increases Its Binding to the Human Neonatal Fc Receptor in Vitro |
| Creator | Brachet et al. |
| Author | Guillaume Brachet |
| Author | Renaud Respaud |
| Author | Christophe Arnoult |
| Author | Corinne Henriquet |
| Author | Christine Dhommée |
| Author | Marie-Claude Viaud-Massuard |
| Author | Nicolas Joubert |
| Author | Martine Pugnière |
| Author | Valérie Gouilleux-Gruart |
| Abstract | Antibody-drug conjugates, such as brentuximab vedotin (BTXv), are an innovative category of monoclonal antibodies. BTXv is bioconjugated via the chemical reduction of cysteine residues involved in disulfide bonds. Species of BTXv containing zero, two, four, six, or eight vedotin molecules per antibody coexist in the stock solution. We investigated the influence of drug loading on the binding of the antibody to FcRn, a major determinant of antibody pharmacokinetics in humans. We developed a hydrophobic interaction chromatography (HIC) method for separating the different species present in the stock solution of BTXv, and we purified and characterized the collected species before use. We assessed the binding of these different species to FcRn in a cellular assay based on flow cytometry and surface plasmon resonance. HIC separated the different species of BTXv and allowed their collection at adequate levels of purity. Physicochemical characterization showed that species with higher levels of drug loading tended to form more aggregates. FcRn binding assays showed that the most conjugated species, particularly those with saturated loading, interacted more strongly than unconjugated BTXv with the FcRn. |
| Publication | Molecular Pharmaceutics |
| Volume | 13 |
| Issue | 4 |
| Pages | 1405-1412 |
| Date | Apr 04, 2016 |
| Journal Abbr | Mol. Pharm. |
| Language | eng |
| DOI | 10.1021/acs.molpharmaceut.6b00082 |
| ISSN | 1543-8392 |
| Library Catalog | PubMed |
| Extra | PMID: 26900766 |
| Tags | Antibodies, Monoclonal, antibody?drug conjugate, author, Chromatography, Gel, drug-to-antibody ratio, FcRn, Flow Cytometry, Histocompatibility Antigens Class I, Humans, Hydrophobic and Hydrophilic Interactions, hydrophobic interaction chromatography, Immunoconjugates, original, pp2i, Protein Binding, Receptors, Fc, Surface Plasmon Resonance |
| Date Added | 2019/06/04 - 17:29:34 |
| Date Modified | 2020/01/14 - 10:26:38 |
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