Thursday, April 24, 2014
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Mice with directed
integration of human immunoglobulin transgenes to produce chimeric antibodies
with fully human variable domains
Transgenic mice that
produce chimeric antibodies with fully human variable domains could be used
to discover therapeutic antibodies. In mouse embryonic stem cells, the entire
human immunoglobulin variable gene repertoire was inserted into the
corresponding mouse loci, and endogenous mouse variable genes were silenced.
The resulting transgenic mice had functional immune systems that when
injected with a human CD40
antigen or a Staphylococcus aureus a-hemolysin
antigen produced antibodies with neutralization capacity comparable to or
more potent than that of the anti-CD40L antibody 5C8
or anti-aHL antibody KBSA301.
Next steps could include testing eight different antibodies produced by the
transgenic mice in animal models of disease.
Biogen Idec Inc. has 5C8 in Phase
I testing to treat systemic lupus erythematosus (SLE).
Kenta Biotech Ltd. has KBSA301 in
Phase I/II trials to treat pneumonia and Phase I testing to treat Staphylococcus
Published online April 24, 2014
Patented; available for
Lee, E.-C. et al. Nat.
Biotechnol.; published online March 16, 2014;
Contact: Allan Bradley, Kymab Ltd., Cambridge, U.K.
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