Methods for treating glioblastoma
Aspects of the disclosure relate to a method of treating glioblastoma in a subject comprising administering to the subject a KDM6B inhibitor. In some aspects, the methods are performed in combination with an immunotherapy. Further aspects relate to a composition comprising a KDM6B inhibitor and an immunotherapy.
1 . A method of treating refractory glioblastoma in a subject comprising administering to the subject a small molecule KDM6B inhibitor comprising GSK-J4 or a myeloid cell treated with the small molecule KDM6B inhibitor comprising GSK-J4, and an immunotherapy comprising an immune checkpoint blockade (ICB) therapy comprising anti-PD-1 or anti-PDL1 therapy.
2 . The method of claim 1 , wherein the glioblastoma is further defined as glioblastoma with myeloid infiltration.
3 . The method of claim 1 , wherein the myeloid cells are isolated from bone marrow cells from the subject or from a bone marrow donor.
4 . The method of claim 1 , wherein the ICB therapy comprises a monotherapy or a combination ICB therapy.
5 . The method of claim 1 , wherein the ICB therapy further comprises an inhibitor of PDL2, CTLA-4, B7-1, and/or B7-2.
6 . The method of claim 5 , wherein the ICB therapy further comprises an anti-CTLA-4 monoclonal antibody.
7 . The method of claim 1 , wherein the ICB therapy comprises one or more of nivolumab, pembrolizumab, pidilizumab, ipilimumab, and tremelimumab.
8 . The method of claim 1 , wherein the subject has been previously treated for glioblastoma with an anticancer agent.
9 . The method of claim 8 , wherein the previous treatment comprises an immunotherapy.
10 . The method of claim 9 , wherein the subject has been determined to be non-responsive to the previous therapy.
11 . The method of claim 1 , wherein the method further comprises administering at least one additional anticancer treatment.
12 . The method of claim 11 , wherein the small molecule KDM6B inhibitor, immunotherapy, and/or at least one additional anticancer agent is administered intravenously.