Non-viral adeno-associated virus-based platform for stable expression of antibody combination therapeutics
Autor: | Ethan Clark, Gwendolyn M Wilmes, Rachel S Quesenberry, Sergey V Shulga-Morskoy, Violetta Medik, Stuart W. Hicks, Megan E Lewis, Stephen R Lutz, Anthony B Cooper, Hugh H. Russell, Elizabeth E. Reczek, Paulina Kocjan, Jesse A Stevenson, Kimberly L Carey |
---|---|
Rok vydání: | 2014 |
Předmět: |
medicine.drug_class
Cell Immunology Gene Expression medicine.disease_cause Monoclonal antibody law.invention Cell Line law Report Gene expression medicine Humans Immunology and Allergy Adeno-associated virus biology Dependovirus Chromatography Ion Exchange Virology Coculture Techniques Recombinant Proteins medicine.anatomical_structure Cell culture biology.protein Recombinant DNA Drug Therapy Combination Antibody Single-Chain Antibodies |
Zdroj: | mAbs |
ISSN: | 1942-0862 1942-0870 |
DOI: | 10.4161/mabs.28917 |
Popis: | Antibody combination therapeutics (ACTs) are polyvalent biopharmaceuticals that are uniquely suited for the control of complex diseases, including antibiotic resistant infectious diseases, autoimmune disorders and cancers. However, ACTs also represent a distinct manufacturing challenge because the independent manufacture and subsequent mixing of monoclonal antibodies quickly becomes cost prohibitive as more complex mixtures are envisioned. We have developed a virus-free recombinant protein expression platform based on adeno-associated viral (AAV) elements that is capable of rapid and consistent production of complex antibody mixtures in a single batch format. Using both multiplexed immunoassays and cation exchange (CIEX) chromatography, cell culture supernatants generated using our system were assessed for stability of expression and ratios of the component antibodies over time. Cultures expressing combinations of three to ten antibodies maintained consistent expression levels and stable ratios of component antibodies for at least 60 days. Cultures showed remarkable reproducibility following cell banking, and AAV-based cultures showed higher stability and productivity than non-AAV based cultures. Therefore, this non-viral AAV-based expression platform represents a predictable, reproducible, quick and cost effective method to manufacture or quickly produce for preclinical testing recombinant antibody combination therapies and other recombinant protein mixtures. |
Databáze: | OpenAIRE |
Externí odkaz: |