Humanized mouse models for assessing immune cell therapy
AssigneeThe Jackson Laboratory
InventorsJames Keck, Jing Jiao, Chunting Ye
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Abstract
Provided herein are humanized mouse models and methods for determining whether administration of engineered immune cell therapies likely elicit cytokine release syndrome and/or determining the efficacy of an anti-disease therapy. Further, the models provided herein may be used to test the efficacy of different anti-CRS therapies.
Claims15
-44. (canceled)
A non-obese diabetic mouse whose genome comprises a null Prkdc gene, a null Il2rg gene, a null MHC Class I H2-K1 gene, a null MHC Class I H2-D1 gene, and a null MHC Class II H2-Ab1 gene, wherein:
- the mouse has been irradiated and engrafted with (i) human tumor cells that express a cell surface antigen and (ii) human peripheral blood mononuclear cells (PBMCs),
- the mouse comprises human cells selected from T cells, B cells, Natural Killer cells, and monocytes that have developed from the human PBMCs, and
- the mouse comprises human cytokines secreted by the human cells.
A non-obese diabetic mouse whose genome comprises a null Prkdc gene, a null Il2rg gene, a null MHC Class I H2-K1 gene, a null MHC Class I H2-D1 gene, and a null MHC Class II H2-Ab1 gene,
- wherein the mouse has been irradiated and engrafted with
- (i) human tumor cells that express a cell surface antigen and
- (ii) human peripheral blood mononuclear cells (PBMCs), and
- wherein the mouse comprises
- (iii) human cells selected from T cells, B cells, Natural Killer cells, and monocytes that have developed from the human PBMCs,
- (iv) human cytokines secreted by the human cells selected from IL-6, IL-10, IFN-γ, MCP-1, GM-CSF, TNF, IL-1, IL-2, IL-2Rα, IL-8, IL-4, IL-18, and MIP-4, and
- (v) engineered human T cells that express a chimeric antigen receptor that specifically binds to the cell surface antigen.
Dependencies are inferred from the claim text.