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A new approach to produce IgG4-like bispecific antibodies.
- Source :
-
Scientific Reports . 9/20/2021, Vol. 11 Issue 1, p1-12. 12p. - Publication Year :
- 2021
-
Abstract
- While achieving rapid developments in recent years, bispecific antibodies are still difficult to design and manufacture, due to mispair of both heavy and light chains. Here we report a novel technology to make bispecific molecules. The knob-into-hole method was used to pair two distinct heavy chains as a heterodimer. IgG4 S228P CH1-CL interface was then partially replaced by T-cell receptor α/β constant domain to increase the efficiency of cognate heavy and light chain pairing. Following expression and purification, the bispecific antibody interface exchange was confirmed by Western blotting and LC–MS/MS. To ensure its validity, we combined a monovalent bispecific antibody against PD-1 (sequence from Pembrolizumab) and LAG3 (sequence from Relatlimab). The results showed that the molecule could be assembled correctly at a ratio of 95% in cells. In vitro functional assay demonstrated that the purified bispecific antibody exhibits an enhanced agonist activity compared to that of the parental antibodies. Low immunogenicity was predicted by an open-access software and ADA test. [ABSTRACT FROM AUTHOR]
- Subjects :
- *IMMUNOGLOBULIN G
*HETERODIMERS
*T cell receptors
*PROTEIN expression
*PEMBROLIZUMAB
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 11
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Scientific Reports
- Publication Type :
- Academic Journal
- Accession number :
- 152535557
- Full Text :
- https://doi.org/10.1038/s41598-021-97393-2