US 12,409,237 B1
Methods and models for assessing efficacy of immunotherapies
Leonard D. Shultz, Bar Harbor, ME (US); James Keck, Bar Harbor, ME (US); Dale L. Greiner, Westborough, MA (US); and Michael A. Brehm, Westborough, MA (US)
Assigned to The Jackson Laboratory, Bar Harbor, ME (US); and University of Massachusetts, Westborough, MA (US)
Filed by The Jackson Laboratory, Bar Harbor, ME (US); and University of Massachusetts, Westborough, MA (US)
Filed on Jun. 28, 2024, as Appl. No. 18/758,838.
Application 18/758,838 is a continuation of application No. 16/465,006, previously published as PCT/US2017/063948, filed on Nov. 30, 2017.
Claims priority of provisional application 62/565,783, filed on Sep. 29, 2017.
Claims priority of provisional application 62/428,131, filed on Nov. 30, 2016.
This patent is subject to a terminal disclaimer.
Int. Cl. A01K 67/0278 (2024.01); A01K 67/0271 (2024.01); A61K 49/00 (2006.01)
CPC A61K 49/0008 (2013.01) 10 Claims
 
1. A method for assessing anti-tumor efficacy of an immunotherapy, the method comprising:
administering an immunotherapy to an immunodeficient transgenic mouse whose genome expresses a transgene encoding human stem cell factor (hSCF), a transgene encoding human granulocyte-macrophage colony-stimulating factor (hGM-CSF), a transgene encoding human interleukin-3 (hIL-3), and a transgene encoding human colony-stimulating factor 1 (hCSF1), wherein the immunodeficient transgenic mouse has been humanized and engrafted with a human tumor xenograft, wherein the immunodeficient transgenic mouse (a) comprises fewer numbers of human CD20+ cells and increased numbers of human CD3+ cells, CD33+ cells, CD14+ cells, and CD56+ cells as a proportion of human CD45+ cells relative to a control mouse, (b) displays an increase in the relative number of human CD14+ macrophages and human CD56+ natural killer cells and increased concentrations of macrophage-secreted cytokines relative to a control mouse, and (c) the control mouse is an immunodeficient transgenic mouse whose genome expresses a transgene encoding hSCF, a transgene encoding hGM-CSF, and a transgene encoding hIL-3, and not a transgene encoding hCSF1; and
assessing anti-tumor efficacy of the immunotherapy.