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Large scale production of recombinant human lactoferrin in the milk of transgenic cows

Nature Biotechnology volume 20, pages 484–487 (2002)Cite this article

Abstract

The limited capacity of current bioreactors has led the biopharmaceutical industry to investigate alternative protein expression systems. The milk of transgenic cattle may provide an attractive vehicle for large-scale production of biopharmaceuticals, but there have been no reports on the characteristics of such recombinant proteins. Here we describe the production of recombinant human lactoferrin (rhLF), an iron-binding glycoprotein involved in innate host defense, at gram per liter concentrations in bovine milk. Natural hLF from human milk and rhLF had identical iron-binding and -release properties. Although natural hLF and rhLF underwent differential N-linked glycosylation, they were equally effective in three different in vivo infection models employing immunocompetent and leukocytopenic mice, and showed similar localization at sites of infection. Taken together, the results illustrate the potential of transgenic cattle in the large-scale production of biopharmaceuticals.

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Figure 1: Characterization of rhLF isolated from bovine milk.
Figure 2: Effect of rhLF and natural hLF on experimentally induced infections in mice.
Figure 3: Scintigrams for 99mTc-labeled rhLF and 99mTc-labeled natural hLF in mice infected (thigh muscle) with multidrug-resistant S. aureus.

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Acknowledgements

We wish to acknowledge all the colleagues at Pharming who contributed to the lactoferrin project. We thank J. Kamerling and G. Gerwig (University of Utrecht, The Netherlands) for the monosaccharide composition analysis.

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Authors and Affiliations

  1. Pharming, Leiden, The Netherlands

    Patrick H.C. van Berkel, Marlieke Geerts, Harry A. van Veen, Mourad Salaheddine, Frank Pieper & Jan H. Nuijens

  2. Department of Radiology, Division of Nuclear Medicine, Leiden University Medical Center, Leiden, The Netherlands

    Mick M. Welling & Ernest K. J. Pauwels

  3. Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands

    Bep Ravensbergen & Peter H. Nibbering

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  1. Patrick H.C. van Berkel
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  2. Mick M. Welling
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Correspondence to Patrick H.C. van Berkel.

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Competing interests

The authors are employed by Pharming. Pharming is a biotechnology company, developing human lactoferrin as one of their products.

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van Berkel, P., Welling, M., Geerts, M. et al. Large scale production of recombinant human lactoferrin in the milk of transgenic cows. Nat Biotechnol 20, 484–487 (2002). https://doi.org/10.1038/nbt0502-484

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