CD4+ OX40+ Foxp3+ Lymphocyte Assay for Cancer Prognosis
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Solution Overview
Problem
There is a need for diagnostic, prognostic, and predictive methods to identify patients who would benefit from anti-tumor treatments that modulate OX40 activity, as increased intratumoral Treg cell densities are associated with poor prognosis in various cancers.
Innovation Solution
The method involves measuring the number of CD4+ OX40+ Foxp3+ lymphocytes in cancer samples and using this information to determine prognosis, predict responsiveness to OX40 agonist treatment, and administer an effective amount of an OX40 agonist if the number is higher than a reference, thereby potentially improving overall and progression-free survival.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-tumor treatments that modulate OX40 activity are administered, then patient prognosis may improve, but it is difficult to identify which patients will benefit without precise diagnostic methods
Solution Approach 1:
The patent replaces complex manual diagnostic evaluation with automated flow cytometry-based detection systems. The method uses standardized immunophenotyping protocols with fluorescently labeled antibodies to detect OX40+ Treg cells, transforming subjective clinical assessment into objective, quantifiable data that can be processed automatically by flow cytometers, thereby improving reliability while reducing operational complexity
Solution Approach 2:
The patent establishes specific threshold parameters for OX40+ Treg cell frequencies that predict treatment response. By defining quantitative cutoff values (e.g., frequency thresholds for predicting checkpoint inhibitor responsiveness), the patent converts continuous cellular measurement data into discrete prognostic categories, enabling simplified clinical decision-making based on measurable parameter changes
2Object-generated harmful factors
If intratumoral Treg cell densities are increased, then immune suppression is enhanced, but this leads to poor patient prognosis
Solution Approach 1:
The patent converts the harmful presence of OX40+ Treg cells into a beneficial diagnostic marker. By detecting and quantifying these cells that normally suppress immunity, the method identifies patients who are likely to respond to OX40-modulating therapies. The very cells that cause immune suppression become the basis for selecting patients who will benefit from treatments designed to reverse this suppression
Solution Approach 2:
The patent creates a feedback loop where measurement of OX40+ Treg cell levels informs treatment decisions, which then modify the immune environment, potentially changing the Treg cell populations. This feedback mechanism allows dynamic adjustment of therapy based on measurable immune parameters, converting the initially harmful Treg cell presence into a controllable variable that can be targeted therapeutically
Data Source
AI summary
The present disclosure provides methods for measuring the number of CD4+ OX40+ Foxp3+ lymphocytes in a sample containing cancer cells and lymphocytes obtained from a subject by labeling lymphocytes that show CD4 expression in the sample, then labeling lymphocytes that show OX40 expression in the sample, then labeling lymphocytes that show Foxp3 expression in the sample, then measuring the number of CD4+ OX40+ Foxp3+ lymphocytes in the sample. Further provided are methods for determining the prognosis of a subject, predicting responsiveness of a subject having cancer to an OX40 agonist treatment, and methods for treating or delaying progression of cancer based on the number of CD4+ OX40+ Foxp3+ lymphocytes in a sample.