Productive common light chain libraries yield diverse panels of high affinity bispecific antibodies
| العنوان: | Productive common light chain libraries yield diverse panels of high affinity bispecific antibodies |
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| المؤلفون: | Thomas Van Blarcom, Surabhi Srinivasan, Cendy Valle Oseguera, Sheng Ding, Arvind Rajpal, Purnima Sundar, Yu Yan, Dan McDonough, Zygy Roe-Zurz, Meri Galindo Casas, Wai Ling Cheung, Zea Melton, Shobha Potluri, Javier Chaparro-Riggers, Kevin Lindquist, Wagstrom Christopher R, Wenwu Zhai, Jaume Pons, Andrea Rossi, Steven J. Pitts, Jeffrey Jones, Marina Sirota |
| المصدر: | mAbs, vol 10, iss 2 mAbs |
| بيانات النشر: | Informa UK Limited, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Bispecific antibody, medicine.drug_class, T cell, Immunology, Computational biology, Protein Engineering, Monoclonal antibody, Immunoglobulin light chain, Antibodies, Epitope, 4-1BB, Mice, 03 medical and health sciences, synthetic antibody library, 0302 clinical medicine, Antigen, Peptide Library, Report, Antibodies, Bispecific, medicine, Animals, Humans, Immunology and Allergy, Purification methods, biology, common light chain, Chemistry, high affinity, Pharmacology and Pharmaceutical Sciences, bispecific antibody, manufacturing, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Public Health and Health Services, biology.protein, Bispecific, Immunoglobulin Light Chains, Immunization, Antibody, Biotechnology |
| الوصف: | The commercial success of bispecific antibodies generally has been hindered by the complexities associated with generating appropriate molecules for both research scale and large scale manufacturing purposes. Bispecific IgG (BsIgG) based on two antibodies that use an identical common light chain can be combined with a minimal set of Fc mutations to drive heavy chain heterodimerization in order to address these challenges. However, the facile generation of common light chain antibodies with properties similar to traditional monoclonal antibodies has not been demonstrated and they have only been used sparingly. Here, we describe the design of a synthetic human antibody library based on common light chains to generate antibodies with biochemical and biophysical properties that are indistinguishable to traditional therapeutic monoclonal antibodies. We used this library to generate diverse panels of well-behaved, high affinity antibodies toward a variety of epitopes across multiple antigens, including mouse 4-1BB, a therapeutically important T cell costimulatory receptor. Over 200 BsIgG toward 4-1BB were generated using an automated purification method we developed that enables milligram-scale production of BsIgG. This approach allowed us to identify antibodies with a wide range of agonistic activity that are being used to further investigate the therapeutic potential of antibodies targeting one or more epitopes of 4-1BB. |
| وصف الملف: | application/pdf |
| تدمد: | 1942-0870 1942-0862 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2f1ac7599bc9d5358987352dc6408d94 https://doi.org/10.1080/19420862.2017.1406570 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2f1ac7599bc9d5358987352dc6408d94 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 19420870 19420862 |
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