Thursday, April 10, 2014
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Mice with human innate
Humanized mice with
functional human innate immune cells could be used as models to study cancer
in the presence of an intact human immune system. Previous humanized mouse
models could not support development of human monocytes, macrophages or NK
cells. In immunodeficient mice expressing human macrophage
colony-stimulating factor 1 (CSF1;
macrophage colony-stimulating factor (GM-CSF;
regulatory protein-a (SIRPA),
irradiation followed by transplantation of human fetal liver- or
progenitor cells resulted in development of functional human monocytes,
macrophages and NK cells but led to the destruction of red blood cells, which
caused anemia within two to three weeks. In mice with functional human
monocytes, macrophages and NK cells, compared with mice lacking such cells,
engrafted human melanoma tumors showed increased infiltration by human
macrophages and decreased tumor volume. Ongoing work includes using the mice
to evaluate the behavior of hematologic malignancies, solid tumors and
Published online April 10, 2014
Patent application filed;
available for licensing
Rongvaux, A. et al. Nat.
Biotechnol.; published online March 16, 2014;
Contact: Richard A. Flavell, Yale University, New Haven, Conn.
Contact: Markus G. Manz, University Hospital Zurich, Zurich,
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