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Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG.
- Source :
-
Nature communications [Nat Commun] 2015 Feb 12; Vol. 6, pp. 6113. Date of Electronic Publication: 2015 Feb 12. - Publication Year :
- 2015
-
Abstract
- Bispecific antibodies enable unique therapeutic approaches but it remains a challenge to produce them at the industrial scale, and the modifications introduced to achieve bispecificity often have an impact on stability and risk of immunogenicity. Here we describe a fully human bispecific IgG devoid of any modification, which can be produced at the industrial scale, using a platform process. This format, referred to as a κλ-body, is assembled by co-expressing one heavy chain and two different light chains, one κ and one λ. Using ten different targets, we demonstrate that light chains can play a dominant role in mediating specificity and high affinity. The κλ-bodies support multiple modes of action, and their stability and pharmacokinetic properties are indistinguishable from therapeutic antibodies. Thus, the κλ-body represents a unique, fully human format that exploits light-chain variable domains for antigen binding and light-chain constant domains for robust downstream processing, to realize the potential of bispecific antibodies.
- Subjects :
- Antibodies, Monoclonal metabolism
Chromatography, High Pressure Liquid
Humans
Immunoglobulin Light Chains metabolism
Immunoglobulin kappa-Chains metabolism
Neutralization Tests
Peptide Library
T-Lymphocytes immunology
Antibodies, Bispecific isolation & purification
Immunoglobulin G isolation & purification
Immunoglobulin Heavy Chains isolation & purification
Protein Engineering methods
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 25672245
- Full Text :
- https://doi.org/10.1038/ncomms7113