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Disease models

Mice with human innate immune cells

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; M-CSF), IL-3, granulocyte macrophage colony-stimulating factor (GM-CSF; CSF2), thrombopoietin (TPO) and signal regulatory protein-a (SIRPA), irradiation followed by transplantation of human fetal liver- or adult-derived CD34+ 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 autoimmune diseases.

SciBX 7(14); doi:10.1038/scibx.2014.411
Published online April 10, 2014

Patent application filed; available for licensing

Rongvaux, A. et al. Nat. Biotechnol.; published online March 16, 2014;
doi:10.1038/nbt.2858
Contact: Richard A. Flavell, Yale University, New Haven, Conn.
e-mail:

richard.flavell@yale.edu
Contact: Markus G. Manz, University Hospital Zurich, Zurich, Switzerland
e-mail:

markus.manz@usz.ch