Taking the Hinge off: An Approach to Effector-Less Monoclonal Antibodies
| Autor: | James Woo, Manu Kanwar, Jenny Wang, Dan Boyd, Alexandre Ambrogelly, Daniel Stenzel, Jamie Valeich, Deblina De Ghosh, Arpa Ebrahimi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy Antibody-dependent cellular cytotoxicity (ADCC) medicine.drug_class Immunology Hinge FcγRI Monoclonal antibody Article Domain (software engineering) 03 medical and health sciences 0302 clinical medicine Drug Discovery medicine Immunology and Allergy Gene silencing FcγRIII Effector functions hinge Receptor Target antigen mAb IgG4 Fcγ receptors Effector Chemistry IgG1 Cell biology FcRn 030104 developmental biology monoclonal antibody Fc neonatal receptor lcsh:RC581-607 Fab arm exchange 030215 immunology effector function |
| Zdroj: | Antibodies Volume 9 Issue 4 Antibodies, Vol 9, Iss 50, p 50 (2020) |
| ISSN: | 2073-4468 |
| Popis: | A variety of Fc domain engineering approaches for abrogating the effector functions of mAbs exists. To address some of the limitations of the current Fc domain silencing approaches, we are exploring a less commonly considered option which relies on the deletion of the hinge. Removal of the hinge domain in humanized IgG1 and IgG4 mAbs obliterates their ability to bind to activating human Fc gamma receptors I and IIIA, while leaving their ability to engage their target antigen intact. Deletion of the hinge also reduces binding to the Fc neonatal receptor, although Fc engineering allows partial recovery of affinity. Engineering of the CH3 domain, stabilizes hinge deleted IgG4s and prevents Fab arm exchange. The faster clearing properties together with the pacified Fc make modality of the hinge deleted mAb an appealing solution for therapeutic and diagnostic applications. |
| Databáze: | OpenAIRE |
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