Research abstract

Article abstract


Nature Biotechnology 27, 173 - 181 (2009)
Published online: 18 January 2009 | doi:10.1038/nbt.1521

Antigen-specific human polyclonal antibodies from hyperimmunized cattle

Yoshimi Kuroiwa1,2, Poothappillai Kasinathan1, Thillainayagen Sathiyaseelan1, Jin-an Jiao1, Hiroaki Matsushita1, Janaki Sathiyaseelan1, Hua Wu1, Jenny Mellquist1, Melissa Hammitt1, Julie Koster1, Satoru Kamoda2, Katsumi Tachibana2, Isao Ishida2 & James M Robl1


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 κ-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 κ-light chain (up to ~650 μg/ml, fully human) or with bovine κ- or λ-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.

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  1. Hematech, Inc, 4401 S. Technology Dr., Sioux Falls, South Dakota 57106, USA.
  2. Kyowa Hakko Kirin Co., Ltd., 1-6-1 Ohtemachi, Chiyoda-ku, Tokyo 100-8185, Japan.

Correspondence to: James M Robl1 e-mail: jrobl@hematech.com

Correspondence to: Yoshimi Kuroiwa1,2 e-mail: ykuroiwa@hematech.com



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