THE USE OF OXYGEN CARRIERS FOR INCREASING THE PRODUCTION OF MONOCLONAL-ANTIBODIES FROM HOLLOW-FIBER BIOREACTORS

The use of chemical oxygen carriers to enhance growth and monoclonal a ntibody production of hybridomas in hollow fibre bioreactor systems wa s investigated. These oxygen carriers include natural bovine haemoglob in, Erythrogen(TM)-1, Formula-1(TM), polyethylene glycol cross-linked haemoglobin, and perfluorocarbon emulsion. Their solutions were tested in static cell culture for material evaluation and subsequently inves tigated for their ability to increase the cell growth rate and product ion levels in hollow fibre bioreactor systems. Oxygen carriers were ad ded to the medium reservoir of 0.14 m(2) (research scale) hollow fibre bioreactors to test for any increases in culture performance using ty pical production protocols. Stabilized and cross-linked haemoglobin ad ditives caused an increase in the output of antibody over controlled c ultures with no additive. No increase in production was observed for n atural bovine haemoglobin. Production enhancements ranged from 104% us ing Erythrogen to 20% using the polyethylene glycol cross-linked-haemo globin. The perfluorocarbon emulsion demonstrated a 78 % increase rela tive to the control. A ratio of lactate production rate to glucose con sumption rate (LPR/GUR) was used as a measure of the efficiency of oxy gen usage. Haemoglobin additives that resultted in an increase in anti body output were found to decrease the ratio in an inversely proportio nal manner.