Resistance to checkpoint blockade therapy
AssigneeThe General Hospital Corporation
InventorsNir Hacohen, Moshe Sade-Feldman
Life of this patent
Estimating the term…
Abstract
Provided herein are methods of determining resistance to checkpoint blockade (CPB) therapy in a cancer patient, methods of typing tumor cells of a cancer patient, methods of assigning treatment to a cancer patient and methods of treatment of a cancer patient based on determining in a tumor sample of said patient, reduced expression of a gene relating to antigen processing pathway or a product thereof, or a modification causing said reduced expression, wherein the presence of said reduced expression or modification is indicative of resistance to CPB therapy.
Claims12
A method for treating cancer in a patient resistant to CPB therapy, said method comprising:
- detecting, in a tumor sample from the patient, one or more genetic modifications in the B2M gene, wherein the one or more genetic modifications are selected from the group consisting of:
- the combination of a p.Leu13fs and p.Ser14fs frame-shift mutation, the combination of a p.Gly63fs and p.Ser14fs frame-shift mutation, a p.Leu13fs frame-shift mutation, and a p.Gly63fs frame-shift mutation;
- treating the patient with a CPB therapy if the one or more genetic modifications are not detected, or treating the patient with a therapy other than CPB therapy if the one or more genetic modifications are detected.
A method for treating cancer in a patient resistant to CPB therapy, said method comprising:
- staining a tumor sample from the patient for B2M protein and one or more markers specific to tumor cells;
- determining the expression of B2M protein based on B2M staining in tumor cells stained by the one or more markers specific to tumor cells, wherein the B2M expression is scored based on the percentage of B2M expressing cells in the tumor fraction, such that Minimal is 0-10%;
- Low is 10-50%;
- Intermediate is 50-80%;
- and High is 80-100%;
- and
- treating the patient with a CPB therapy if B2M expression is Low, Intermediate, or High, or treating the patient with a therapy other than CPB therapy if B2M is Minimal.
Dependencies are inferred from the claim text.