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AssigneeAugusta University Research Institute, Inc.
InventorsSamir N. Khleif, Vivek Verma, Seema Gupta
Estimating the term…
Compositions and methods of their use to detect and treat anti-PD1 therapy resistance are provided herein. Compositions that immunospecifically bind and deplete dysfunctional T cells are provided. The dysfunctional T cells that are depleted include CD38+PD-1+ T cells, CD38+CD8+ T-cells, or both. The dysfunctional T cells can be depleted, for example, by administering an antibody or fusion protein that specifically binds to dysfunctional T cells and promotes their depletion. In one embodiment the antibody is a bispecific antibody that can be specific for CD38 and CD8, or it can be specific for CD38 and PD-1. Also disclosed is a method of detecting and treating anti-PD1 therapy resistance by measuring the amount of CD38+PD1+CD8 T cells in blood or tissue samples obtained from a subject prior to anti-PD1 therapy and administering an anti-CD38/CD8 or anti-CD38/PD-1 depleting/blocking antibody to the subject prior to anti-PD1 therapy.
A method of reducing tumor burden in a subject in need thereof comprising:
A method of increasing the efficacy of anti-PD-1/PD-L1 therapy in a subject in need thereof comprising:
A method of detecting and treating resistance to anti-PD1/PDL1 therapy in a subject in need thereof, the method comprising:
A kit for detecting and treating anti-PD1/PDL1 resistance in a subject comprising;
A method of reversing resistance to or enhancing the efficacy of immune therapy in a subject in need thereof, comprising administering to the subject a composition comprising a compound that downregulates or inhibits the biological activity of CD38 by an amount effective to enhance cell activation, proliferation, and effector functions of CD8+ T cells in an amount effective to reverse resistance or enhance the efficacy of immune therapy.
Dependencies are inferred from the claim text.