Methods of determining an immune response score
Inventors
Bacus, Sarah S. • Hamm, Christopher A.
Assignees
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Publication Number
US-10851422-B2
Publication Date
2020-12-01
Expiration Date
Abstract
The present disclosure provides method for determining an immune response score (irScore), the method comprising: determining a number of differentially expressed genes that have are implicated in anti-tumor immune cell signaling/activation; determining a number of differentially expressed genes that are implicated in immunosuppression, wherein the irScore=X(low, medium, or high), wherein X is the number of differentially expressed genes that are implicated in anti-tumor immune cell signaling/activation, and wherein low refers to 1-4 differentially expressed genes that are implicated in immunosuppression, medium refers to 5-9 differentially expressed genes that are implicated in immunosuppression, and high refers to 10 or more differentially expressed genes that are implicated in immunosuppression.
Core Innovation
The invention provides a method for treating a subject with an anticancer immunotherapy by using an immune response score (irScore) derived from gene expression in a biological sample. The method includes obtaining a biological sample, determining a number of expressed genes implicated in anti-tumor immune cell signaling/activation, and determining a number of expressed genes implicated in immunosuppression.
An irScore is calculated from the determinations of the anti-tumor immune cell signaling/activation gene count and the immunosuppression gene count, where the irScore is X (low, medium, or high). The ranges are defined such that low refers to 1–4 expressed genes implicated in immunosuppression, medium refers to 5–9 expressed genes implicated in immunosuppression, and high refers to 10 or more expressed genes implicated in immunosuppression.
Treatment is performed with the anticancer immunotherapy where the irScore meets specified thresholds, including at least 5 for low, 5–25 for medium, and at least 5 for high values as enumerated. The document frames the score as a more uniform approach for immune-tumor microenvironment characterization compared with variable immunohistochemistry (IHC) assays, and it describes an immune gene profiling approach using a targeted immune RNA-seq panel with gene subsets for categories.
Claims Coverage
The document contains one independent claim that defines a treatment method driven by calculating an irScore from counts of expressed genes in two categories. The inventive feature is refined by dependent claims that specify particular immunotherapies and constrain the gene sets using tables.
Immune-response-score–driven treatment using expressed gene counts
A method for treating a subject with an anticancer immunotherapy by obtaining a biological sample, determining a number of expressed genes implicated in anti-tumor immune cell signaling/activation, determining a number of expressed genes implicated in immunosuppression, calculating an irScore from the determinations where the irScore is X (low, medium, or high) and where low refers to 1–4 expressed genes implicated in immunosuppression, medium refers to 5–9 expressed genes implicated in immunosuppression, and high refers to 10 or more expressed genes implicated in immunosuppression, and treating the subject with the immunotherapy where the irScore meets the specified thresholds including at least 5 low, 5 medium, or at least 5 high as enumerated.
Across the independent claim, the core coverage is centered on calculating irScore from category counts of expressed genes (anti-tumor immune cell signaling/activation and immunosuppression) using defined immunosuppression-based ranges (low/medium/high), and administering anticancer immunotherapy when irScore meets the stated thresholds. Dependent claims further narrow the gene sets and/or specify particular immunotherapies and contexts described in the document.
Stated Advantages
Provides an immune response score (irScore) for immune-tumor microenvironment characterization and prediction of response for anticancer immunotherapies.
Proposes a more uniform targeted immune RNA-seq panel approach compared with variable immunohistochemistry (IHC) assays.
Documented Applications
Predicting and treating with anticancer immunotherapies including PD-1 inhibitor, PD-L1 inhibitor, and CTLA4 inhibitor agents such as nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, ipilimumab, and tremelimumab based on an irScore threshold.
Immune-tumor microenvironment characterization in the context of non-small cell lung cancer (NSCLC) using a targeted immune RNA-seq panel approach and immune infiltration comparisons.
An example where tumors are compared as high vs low immune infiltration, yielding a reported set of differentially expressed genes and an irScore example of 35 (medium) based on immune activity and immunosuppression gene categories.
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