Compounds and methods for increasing tumor infiltration by immune cells
AssigneesThe Broad Institute, Inc., President and Fellows of Harvard College, The General Hospital Corporation
InventorsSHRIKANTA CHATTOPADHYAY, STUART L. SCHREIBER
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Abstract
Provided herein are compounds, compositions, and methods that increase the infiltration of tumor cell microenvironments by immune cells. Such methods are useful for enhancing a subject's immune response against the tumor.
Claims28
A combination comprising a GPX4 inhibitor and an immunotherapeutic agent, a lipoxygenase inhibitor, an immunogenic chemotherapeutic agent, or combinations thereof.
4-6. (canceled)
The combination of claim 6, wherein the CTLA4 inhibitor is ipilimumab, the PD1 inhibitor is pembrolizumab or nivolumab, and the PDL1 inhibitor is atezolizumab or durvalumab.
8-16. (canceled)
A method of inducing one or more stromal cells' death, the method comprising contacting the stromal cells with an effective amount of a GPX4 inhibitor.
(canceled)
(canceled)
23-33. (canceled)
35-37. (canceled)
A method of enhancing infiltration of immune cells into a tumor cell's microenvironment, wherein the microenvironment comprises one or more stromal cells, the method comprising contacting the one or more stromal cells with a GPX4 inhibitor. the method further comprising contacting the one or more stromal cells with a GPX4 inhibitor and a lipoxygenase inhibitor.
A method of treating cancer in a subject, the method comprising administering to the subject with a GPX4 inhibitor and a lipoxygenase inhibitor.
43-64. (canceled)
A method of increasing a subject's responsiveness to an immunotherapeutic or immunogenic chemotherapeutic agent, the method comprising administering to the subject in need thereof an effective amount of a GPX4 inhibitor and an effective amount of an immunotherapeutic agent and/or an immunogenic chemotherapeutic agent and/or one or more lipoxygenase inhibitors.
70-77. (canceled)
79-81. (canceled)
Dependencies are inferred from the claim text.