Immunohistochemical assay for detecting expression of programmed death ligand 1 (PD-L1) in tumor tissue
Inventors
Dolled-Filhart, Marisa • EMANCIPATOR, Kenneth • Lynch, Frank • Pierce, Robert H. • Wu, Dianna
Assignees
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Publication Number
US-11193937-B2
Publication Date
2021-12-07
Expiration Date
Abstract
The present disclosure provides processes for describing and quantifying the expression of human programmed death ligand-1 (PD-L1) in tumor tissue sections as detected by immunohistochemical assay using an antibody that specifically binds to PD-L1. The results generated using these processes have a variety of experimental, diagnostic and prognostic applications.
Core Innovation
The document discloses a method for treating a human patient diagnosed with non small cell lung carcinoma (NSCLC) that is driven by a diagnostic report providing one or both of a modified H score (MHS) and a modified P score (MPS) for PD-L1 expression for a tumor sample removed from the patient. A specified threshold is selected from the group consisting of MHS=190, MPS=90, or MHS=190 and MPS=90, and a PD-1 antagonist is administered if one or both of the MHS and the MPS is at or above the specified threshold.
The MHS and MPS are determined by staining a tissue section from the tumor sample in an immunohistochemical (IHC) assay with an anti-PD-L1 antibody that specifically binds human PD-L1. Each tumor nest is examined for staining, and one or both of the MHS and MPS are assigned to the tissue section, with MHS derived from estimated percentages for cells with no staining, weak staining, moderate staining, and strong staining, and MPS derived from the percentage of cells with at least partial membrane staining of any intensity.
The assigning of MHS includes estimating four separate percentages for cells with no staining, weak staining, moderate staining, and strong staining across viable tumor cells and stained mononuclear inflammatory cells in all examined tumor nests, with weak, moderate, and strong requiring at least partial membrane staining and the percentages summing to 100. The estimated percentages are input into the formula MHS=1x(percent of weak staining cells)+2x(percent of moderate staining cells)+3x(percent of strong staining cells), and if both MHS and MPS are assigned, the assignments may be performed in either order or simultaneously.
Claims Coverage
The only independent claim identified is a treatment method for NSCLC based on PD-L1 expression scores determined by PD-L1 immunohistochemistry, with a threshold-based decision to administer a PD-1 antagonist. The independent claim contains three main inventive features.
Threshold-based NSCLC treatment using modified H score and/or modified proportion score for PD-L1
Obtaining a diagnostic report that provides one or both of a modified H score (MHS) and a modified P score (MPS) for PD-L1 expression for a tumor sample removed from the patient; selecting a specified threshold from the group consisting of MHS=190, MPS=90, and MHS=190 and MPS=90; administering a PD-1 antagonist if one or both of the MHS and the MPS is at or above the specified threshold.
IHC-based scoring of modified H score from weak/moderate/strong membrane staining percentages
Determining the MHS by staining a tissue section from the tumor sample in an immunohistochemical (IHC) assay with an antibody that specifically binds to human PD-L1, examining each tumor nest for staining, assigning the MHS by estimating four separate percentages for cells with no staining, weak staining, moderate staining, and strong staining across viable tumor cells and stained mononuclear inflammatory cells in all examined tumor nests, requiring at least partial membrane staining for inclusion in weak/moderate/strong percentages, ensuring the sum equals 100, and inputting the estimated percentages into the formula MHS=1x(percent of weak staining cells)+2x(percent of moderate staining cells)+3x(percent of strong staining cells).
IHC-based scoring of modified proportion score from any-intensity partial membrane staining
Determining the MPS by staining the tissue section in the IHC assay with an anti-PD-L1 antibody, examining each tumor nest for staining, assigning the MPS by estimating across viable tumor cells and mononuclear inflammatory cells in all examined tumor nests the percentage of cells that have at least partial membrane staining of any intensity, with MHS and MPS assignable in either order or simultaneously if both are assigned.
Across the independent claim, the inventive concept is a treatment decision for NSCLC based on PD-L1 expression scores (MHS and/or MPS) that are generated by PD-L1 IHC and quantified from membrane staining, using specified thresholds (MHS=190 and/or MPS=90) to determine when to administer a PD-1 antagonist.
Stated Advantages
Documented Applications
Treating a human patient diagnosed with non small cell lung carcinoma (NSCLC) by administering a PD-1 antagonist based on a diagnostic report providing one or both of MHS and MPS for PD-L1 expression for a tumor sample from the patient.
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