MOLECULAR ROLES OF HSP27 IN IMPROVING MONOCLONAL ANTIBODY PRODUCTION OF CHO CELLS

CHO CELLS ARE THE MAMMALIAN CELL LINES OF CHOICE FOR THE PRODUCTION OF RECOMBINANT THERAPEUTIC BIOLOGICS INCLUDING THE RAPIDLY EXPANDING MONOCLONAL ANTIBODIES (MAB) AND BIOSIMILARS. THERE ARE OPPORTUNITIES TO EXPLORE THE USE OF ENGINEERED CHO CELL LINES WITH IMPROVED RECOMBINANT BIOLOGICS CAPABILITIES. HEAT SHOCK PROTEIN 27 (HSP27) WAS REPORTED TO BE HIGHLY EXPRESSED IN HUMAN CELLS AND HAVE ANTI-CYTOTOXIC FUNCTIONS. HOWEVER, HSP27 EXPRESSION WAS DOWN-REGULATED TOWARDS THE LATE-EXPONENTIAL AND STATIONARY GROWTH PHASE OF CHO FED-BATCH BIOREACTOR CULTURES, MAKING IT A POTENTIAL CELL LINE ENGINEERING TARGET FOR IMPROVING RECOMBINANT BIOLOGICS TITRES IN CHO CELLS. IN THIS THESIS, CHO CELLS WERE ENGINEERED TO OVEREXPRESS HSP27 AND ITS EFFECTS ON CELL GROWTH, MAB PRODUCTION TITRE AND MAB QUALITY UNDER FED-BATCH BIOREACTOR PROCESS WAS ASSESSED. CONCOMITANTLY, HSP27 MOLECULAR ROLES IN IMPROVING CHO FED-BATCH BIOREACTOR CULTURES WERE INVESTIGATED BY PROFILING CASPASE ACTIVITIES, VERIFYING INTERA

Author dc:creator

• TAN GEK LING JANICE

• Apoptosis, Chinese Hamster Ovary (CHO), fed-batch bioreactor, Heat shock protein 27 (HSP27), Monoclonal antibody production