TIME Gene Inhibitors for Solid Tumor Immunotherapy Sensitivity
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Solution Overview
Problem
Current immunotherapy treatments for cancer, such as immune checkpoint blockade, have low response rates due to an incomplete understanding of the tumor immune microenvironment (TIME) and the role of germline factors in tumor sensitivity to host immunity or immunotherapy.
Innovation Solution
The method involves administering an inhibitor of specific TIME genes, such as SLC11A1, CCBL2, LILRB2, or CTSS, to improve sensitivity to immune checkpoint blockade in subjects with solid tumor cancers, thereby enhancing the effectiveness of immunotherapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint blockade is administered to treat solid tumor cancer, then the treatment can activate the immune system against tumors, but the response rate remains low due to incomplete understanding of tumor immune microenvironment and germline factors
Solution Approach 1:
The patent segments the complex tumor immune microenvironment into specific actionable components by identifying individual germline genes (CTSS, CTSW, LYZ, and other TIME genes) that can be independently targeted. This segmentation allows for precise identification of patients with specific germline variants and enables targeted inhibition of particular genes rather than broad, non-specific immunomodulation, thereby improving response rates while reducing the information loss about microenvironmental complexity.
2Reliability
If inhibitors of TIME genes are administered to improve sensitivity to immune checkpoint blockade, then the sensitivity and response rate improve, but the complexity of the treatment regimen increases
Solution Approach 1:
The patent applies preliminary action by performing germline genetic testing to identify specific TIME gene variants (such as CTSS, CTSW, LYZ) before initiating immunotherapy treatment. This preliminary identification of patients with favorable germline profiles allows for pre-selection of candidates who are most likely to benefit from the combination therapy, thereby improving sensitivity to immune checkpoint blockade while managing treatment complexity through risk-stratified patient selection rather than universal complex regimens.
Data Source
AI summary
Provided herein are methods of improving sensitivity to immune checkpoint blockade (ICB) in a subject with a solid tumor cancer, the method comprising: administering to the subject with a solid tumor cancer an inhibitor of a tumor immune microenvironment (TIME) gene, wherein the TIME gene is selected from the group consisting of SLC11A1, CCBL2, LILRB2, LILRB4, LAIR1, CTSS, CTSW, B2M, HAUS1, MS4A4A, FCGR2B, LYZ, and GNPTAB, thereby improving sensitivity to ICB in the subject with a solid tumor cancer.