An Alternative to Transferrin for Cell Culture in Animal-Free Conditions: Recombinant Human Lactoferrin

The use of transferrin in cell culture is a method for providing iron to the cells. The delivery of iron using transferrin has been well documented for cell culture systems and in biomanufacturing of therapeutic proteins, such as monoclonal antibodies. Transferrin is derived from both animal and human serum sources for use in these processes. Recently, a move is being made towards animal and human-free cell culture systems. Iron chelators have been used although many chelators do not control the redox cycling of iron that contributes to oxidative stress. The employment of a human recombinant alternative to transferrin would prove optimal for cell culture as well as for biomanufacturing.

Recombinant human lactoferrin is a 80 kD glycoprotein belonging to the transferrin family of proteins. Lactoferrin has an amino-acid homology and similar iron binding properties to human transferrin. It is present in human milk and epithelial cell surfaces and in blood plasma and tears. Lactoferrin is a multi-functional protein, as such it is a cell growth factor, a source of iron, delays apoptosis and displays anti-microbial properties. Lactoferrin has been reported to have synergistic effects with both EGF (Kohno et al., Acta. Paedietr., 1993) and bFGF on cell growth (Shinoda et al., Adv. Exp. Med. Biol., 1994).

Lacromin™

Lacromin™ (InVitria) is a cell culture grade recombinant human lactoferrin that is produced from an animal-free plant based expression system, ExpressTec (Nandi et al., Transgen. Res., 2005). The ExpressTec system achieves protein expression using the self-pollinating crops of rice and grain. The advantages of ExpressTec include high and stable expression of recombinant proteins, tissue specific expression in grain endosperm, rapid scalability to metric-ton quantities, prevention of Gene flow with self pollinating crops, low capital investment and production costs, and efficient processing and recovery (Huang, BioProcess, 2004). Since Lacromin™ is derived from plants, it is free of any viral or prion contaminant risks.

Lacromin™ has been shown to increase cell growth in many cell lines, including chinese hamster ovary (CHO) cells, human embryonic kidney (HEK) cells and mouse hybridoma cells when compared with transferrin. In hybridoma cells, Lacromin™ increased IgG productivity by 50% compared to transferrin (InVitria Lacromin™ product brochure, www.InVitria.com).

The use of Lacromin™ as a replacement for serum derived transferrin would provide higher cell density and reduction of cell doubling time under animal-free conditions (Haung et al., In Vitro Cell. Dev. Biol.-Animal., 2008). The employment of a human recombinant alternative to transferrin would prove optimal for cell culture as well as for biomanufacturing.

Forbes.com, Press Release: http://www.forbes.com/prnewswire/feeds/prnewswire/2008/10/10/prnewswire200810101418PR_NEWS_USPR_____AQF037.html.