Methods and models for assessing efficacy of immunotherapies

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.