Y. Shi et al., THE USE OF OXYGEN CARRIERS FOR INCREASING THE PRODUCTION OF MONOCLONAL-ANTIBODIES FROM HOLLOW-FIBER BIOREACTORS, Research in immunology (Paris), 149(6), 1998, pp. 576-587
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.