Immunohistochemical proximity assay for PD-1 positive cells and PD-ligand positive cells in tumor tissue
AssigneeMerck Sharp & Dohme Corp.
InventorsRobert H. Pierce, Jennifer H. Yearley, Scott P. Turner, Belma Dogdas, Ansuman Bagchi
Life of this patent
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Abstract
The present disclosure describes an IHC assay for detecting and quantifying spatially proximal pairs of PD-1-expressing cells (PD-1+ cells) and PD-Ligand-expressing cells (PD-L+ cells) in tumor tissue, and the use of the assay to generate proximity biomarkers that are predictive of which cancer patients are most likely to benefit from treatment with a PD-1 antagonist. The disclosure also provides methods for testing tumor samples for the proximity biomarkers, as well as methods for treating subjects with a PD-1 antagonist based on the test results.
Claims18
A method for treating a human patient having a tumor, which comprises:
- (1) obtaining a PD-1:PD-Ligand proximity score for a tumor sample from the patient;
- wherein the PD-1:PD-Ligand proximity score has been assigned to the tumor sample by a process which comprises:
- (a) obtaining an image of tissue that has been removed from the tumor sample and immunohistochemically stained for PD-1 and PD-Ligand expression in a manner that allows stained PD-1 cells to be distinguished from stained PD-Ligand cells;
- (b) defining in the image one or more regions of interest (ROIs) that comprises neoplastic cells and associated stroma, wherein substantially all of the neoplastic cells and associated stroma in the image are contained in the defined ROIs;
- (c) randomly creating across each defined ROI a plurality of subregions of substantially the same shape and size, wherein each of the subregions defines an area that is large enough to include a spatially proximal pair of a stained PD-1 cell and a stained PD-Ligand cell and small enough to exclude pairs of stained PD-1 and PD-Ligand cells that are not spatially proximal;
- and
- (d) calculating the percent of all of the subregions that are positive for both stained PD-1 cells and stained PD-Ligand cells to generate the PD-1:PD-ligand proximity score for the tumor sample,
- (2) comparing the PD-1:PD-Ligand proximity score for the tumor sample with a threshold PD-1:PD-Ligand proximity score,
- (3) classifying the tumor as biomarker positive or biomarker negative,
- wherein if the proximity score for the tumor sample is equal to or greater than the threshold proximity score, then the tumor is classified as positive for the PD-1:PD-Ligand proximity biomarker, and if the obtained score is less than the threshold score, then the tumor is classified as negative for the PD-1:PD-Ligand proximity biomarker, and
- (4) administering to the patient a PD-1 antagonist if the tumor is positive for the PD-1:PD-Ligand proximity biomarker and administering to the subject a cancer treatment that does not include a PD-1 antagonist if the tumor is negative for the PD-1:PD-Ligand proximity biomarker.
Dependencies are inferred from the claim text.