Use of ire1alpha-xbp1 signaling pathway biomarkers for modulating immune responses
AssigneeDana-Farber Cancer Institute, Inc.
InventorsLaurie H. Glimcher, Han Dong
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Abstract
The present invention is based, in part, on the identification of an IRE1α-XBP1-cMyc axis in NK cell immunity. The present invention provides compositions and methods for treating conditions that would benefit from modulating (e.g., upregulating or downregulating) an immune response using an agent that modulates the IRE1α-XBP1 pathway, or a composition comprising modified NK cells.
Claims158
A composition comprising natural killer (NK) cells modified to upregulate the IRE1α-XBP1 pathway.
A method of treating a subject having a condition that would benefit from upregulation of an immune response comprising administering to the subject a therapeutically effective amount of an agent that upregulates the IRE1α-XBP1 pathway such that the condition that would benefit from upregulation of an immune response is treated.
A method of treating a subject having a condition that would benefit from downregulation of an immune response comprising administering to the subject a therapeutically effective amount of an agent that downregulates the IRE1α-XBP1 pathway such that the condition that would benefit from downregulation of an immune response is treated.
A method of assessing the efficacy of an agent that modulates the IRE1α-XBP1 pathway for treating a condition that would benefit from modulating an immune response in a subject, comprising:
- a) detecting in a subject sample at a first point in time the copy number, amount, and/or or activity of at least one biomarker listed in Table 1 in NK cells;
- b) repeating step a) during at least one subsequent point in time after administration of the agent;
- and
- c) comparing the copy number, amount, and/or activity detected in steps a) and b), wherein the presence of, or a significant increase in the copy number, amount, and/or activity of at least one biomarker listed in Table 1 in the subsequent sample as compared to the copy number, amount, and/or activity in the sample at the first point in time, indicates that the agent treats a condition that would benefit from upregulating an immune response in the subject;
- wherein the absence of, or a significant decrease in the copy number, amount, and/or activity of at least one biomarkers listed in Table 1 in the subsequence sample as compared to the copy number, amount, and/or activity in the sample at the first point in time, indicates that the agent treats a condition that would benefit from downregulating an immune response in the subject.
A method of promoting proliferation of NK cells comprising contacting the NK cells with a therapeutically effective amount of an agent that upregulates the IRE1α-XBP1 pathway in the NK cells.
A method of decreasing proliferation of NK cells comprising contacting the NK cells with a therapeutically effective amount of an agent that downregulates the IRE1α-XBP1 pathway in the NK cells.
Dependencies are inferred from the claim text.