BioChem - DOS

High-End pH-controlled delivery of glucose effectively suppresses lactate accumulation in CHO Fed-batch cultures

Biotechnology and bioengineering

Gagnon, Matthew; Hiller, Gregory; Luan, Yen‐ Tung; Kittredge, Amy; DeFelice, Jordy; Drapeau, Denis

<P><B>Abstract</B></P><P>A simple method for control of lactate accumulation in suspension cultures of Chinese hamster ovary (CHO) cells based on the culture's pH was developed. When glucose levels in culture reach a low level (generally below 1&thinsp;mM) cells begin to take up lactic acid from the culture medium resulting in a rise in pH. A nutrient feeding method has been optimized which delivers a concentrated glucose solution triggered by rising pH. We have shown that this high&#8208;end pH&#8208;controlled delivery of glucose can dramatically reduce or eliminate the accumulation of lactate during the growth phase of a fed&#8208;batch CHO cell culture at both bench scale and large scale (2,500&thinsp;L). This method has proven applicable to the majority of CHO cell lines producing monoclonal antibodies and other therapeutic proteins. Using this technology to enhance a 12&#8208;day fed&#8208;batch process that already incorporated very high initial cell densities and highly concentrated medium and feeds resulted in an approximate doubling of the final titers for eight cell lines. The increase in titer was due to additional cell growth and higher cell specific productivity. Biotechnol. Bioeng. 2011; 108:1328&ndash;1337. &copy; 2011 Wiley Periodicals, Inc.</P>

2011

Wiley Subscription Services, Inc., A Wiley Company

0006-3592

1097-0290

108

6

pp.1328-1337

10.1002/bit.23072

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART56794641

CHO cell culture; mammalian cell culture; fed&#x2010; batch; glucose limitation; lactate; monoclonal antibody production;