Design and characterization of mouse IgG1 and IgG2a bispecific antibodies for use in syngeneic models

• Published in: mAbs Vol. 12; no. 1
• Main Authors: Wang, Feng, Tsai, Jordan C., Davis, Jonathan H., Chau, Bryant, Dong, Jia, West, Sean M., Hogan, Jason M., Wheeler, Matthew L., Bee, Christine, Morishige, Winse, Cayton, Thomas, David-brown, Donata, Zhang, Chengyue, Kozhich, Alexander, Sproul, Tim, Dollinger, Gavin, Rajpal, Arvind, Strop, Pavel
• Format: Report
• Language: English
• Published: Taylor & Francis 01.01.2020
• Subjects: co-expression; electrostatic steering; inter-chain disulfide bond shifting; Mouse bispecific antibodies; syngeneic mouse model; T-cell engaging bispecific antibody
• ISSN: 1942-0862; 1942-0870
• DOI: 10.1080/19420862.2019.1685350

The development of antibody therapeutics relies on animal models that accurately recapitulate disease biology. Syngeneic mouse models are increasingly used with new molecules to capture the biology of complex cancers and disease states, and to provide insight into the role of the immune system. The establishment of syngeneic mouse models requires the ability to generate surrogate mouse counterparts to antibodies designed for humans. In the field of bispecific antibodies, there remains a dearth of technologies available to generate native IgG-like mouse bispecific antibodies. Thus, we engineered a simple co-expression system for one-step purification of intact mouse IgG1 and IgG2a bispecific antibodies from any antibody pair. We demonstrated proof of concept with CD3/CD20 bispecific antibodies, which highlighted both the quality and efficacy of materials generated by this technology.