Antigen-specific human polyclonal antibodies from hyperimmunized cattle

DOI PDF Web Site PubMed 被引用文献11件 オープンアクセス

書誌事項

公開日
2009-01-18
権利情報
  • https://www.springernature.com/gp/researchers/text-and-data-mining
  • https://www.springernature.com/gp/researchers/text-and-data-mining
DOI
  • 10.1038/nbt.1521
公開者
Springer Science and Business Media LLC

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説明

Antigen-specific human polyclonal antibodies (hpAbs), produced by hyperimmunization, could be useful for treating many human diseases. However, yields from available transgenic mice and transchromosomic (Tc) cattle carrying human immunoglobulin loci are too low for therapeutic applications. We report a Tc bovine system that produces large yields of hpAbs. Tc cattle were generated by transferring a human artificial chromosome vector carrying the entire unrearranged, human immunoglobulin heavy (hIGH) and kappa-light (hIGK) chain loci to bovine fibroblasts in which two endogenous bovine IgH chain loci were inactivated. Plasma from the oldest animal contained >2 g/l of hIgG, paired with either human kappa-light chain (up to approximately 650 microg/ml, fully human) or with bovine kappa- or lambda-light chain (chimeric), with a normal hIgG subclass distribution. Hyperimmunization with anthrax protective antigen triggered a hIgG-mediated humoral immune response comprising a high proportion of antigen-specific hIgG. Purified, fully human and chimeric hIgGs were highly active in an in vitro toxin neutralization assay and protective in an in vivo mouse challenge assay.

収録刊行物

  • Nature Biotechnology

    Nature Biotechnology 27 (2), 173-181, 2009-01-18

    Springer Science and Business Media LLC

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