PD-1 Response Prediction Using Granzyme B/FOXP3 T-Cell Ratio
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need to monitor and optimize treatment strategies that include blockade of the PD-1 receptor/ligand interaction for treating cancers like melanoma, specifically to identify patients likely to respond to PD-1 binding antagonist antibodies and to rapidly monitor the effectiveness of ongoing treatment.
Innovation Solution
Determine the ratio between Granzyme B+ CD4+ T cells and FOXP3+ CD4+ T cells in a sample from an individual to predict responsiveness to PD-1 binding antagonist antibody treatment, using methods such as immunohistochemistry, flow cytometry, or quantitative PCR to assess protein or mRNA expression levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If PD-1 binding antagonist antibody treatment is administered to treat melanoma, then immune system response is enhanced and tumor cell killing is improved, but treatment effectiveness varies significantly between patients and monitoring is complex
Solution Approach 1:
The patent replaces complex clinical monitoring and immune response assessment with a simplified biomarker-based diagnostic test. By measuring the Granzyme B/FOXP3 ratio through molecular biology techniques, the system substitutes elaborate monitoring procedures with a straightforward quantitative assay that provides reliable prediction of treatment response.
Solution Approach 2:
The patent transforms the complex multidimensional assessment of immune response into a single quantifiable parameter - the Granzyme B/FOXP3 ratio. This parameter change converts difficult-to-measure immune functionality into a simple numerical value that can be easily monitored and used for clinical decision-making.
2Reliability
If comprehensive immune monitoring is performed to identify responders, then treatment optimization is improved, but time required for assessment increases
Solution Approach 1:
The patent extracts the essential predictive information from complex immune monitoring by focusing solely on the Granzyme B/FOXP3 ratio. This extraction principle isolates the critical biomarkers needed for prediction, eliminating unnecessary monitoring steps and reducing assessment time while maintaining high accuracy in identifying treatment responders.
Solution Approach 2:
The patent performs preliminary assessment of the Granzyme B/FOXP3 ratio before initiating PD-1 inhibitor treatment. This preliminary action allows clinicians to predict treatment response in advance, avoiding time-consuming monitoring during treatment and enabling rapid patient selection and treatment optimization.
3Reliability
If multiple biomarkers are measured to predict treatment response, then prediction accuracy is improved, but measurement precision requirements increase
Solution Approach 1:
The patent merges the measurement of two biomarkers (Granzyme B and FOXP3) into a single ratio calculation. By combining these measurements into the Granzyme B/FOXP3 ratio, the system maintains high prediction accuracy while reducing the precision requirements for individual biomarker quantification, as the ratio compensates for variations in individual measurements.
Data Source
Figure 1A~1B
Figure 2
Figure 3A~3B
AI summary
The present invention provides therapeutic and diagnostic methods and compositions for cancer and for enhancing immune function in an individual having cancer. The invention provides methods of treatment, methods for determining whether an individual suffering from a cancer is responding to treatment comprising a PD-1 axis binding antagonist, predicting responsiveness of an individual suffering from a cancer to treatment comprising a PD-1 axis binding antagonist, and methods of selecting a therapy for an individual suffering from cancer.