NOVEL BIOMARKER TO PREDICT EFFICACY OF CANCER IMMUNOTHERAPY

Smart overview of the Invention

A novel biomarker has been developed to predict the efficacy of cancer immunotherapy by analyzing T cell density in paired biopsies taken before and after treatment. This biomarker aims to inform potential outcomes in immunotherapy, particularly in clinical trials. It provides a method to determine if a cancer patient is likely to benefit from immunotherapy by evaluating changes in CD8+ T cell density.

Background

Cancer immunotherapy, which leverages the patient's immune system, has advanced significantly over the past two decades. Checkpoint inhibitors have transformed cancer therapy, but the clinical testing of these drugs presents unique challenges. Unlike traditional treatments, immunotherapy lacks effective pharmacodynamic biomarkers to measure biological effects and predict clinical benefits. There is a need for early markers that can inform potential outcomes before conventional endpoints like overall survival are reached.

Methodology

The invention focuses on the density of CD8+ T cells as a potential early marker of therapeutic efficacy. The inventors examined changes in CD8+ T cell density in paired tumor biopsies from various immunotherapy trials. They demonstrated that a composite decision rule based on CD8+ T cell density correlates with clinical outcomes. Specific cut-off threshold values were identified to predict treatment outcomes, providing a framework for decision-making in cancer immunotherapy.

Applications

This biomarker allows for early prediction of clinical outcomes, reducing unnecessary exposure to ineffective therapies. It benefits both investigational and established cancer therapies by conserving resources and minimizing patient risk. The invention demonstrates a strong association between high CD8 on-treatment density and clinical benefit, using fold-change (FC) and on-treatment density (OTD) as predictive measures.

Conclusion

The composite biomarker captures dynamic changes in CD8+ T cell density, providing a reliable prediction of clinical outcomes. By factoring in both FC and OTD, it mitigates the need for precise biopsy timing and reflects median changes over time. This approach is crucial for informing potential clinical outcomes and optimizing treatment strategies, ensuring that patients receive the most effective therapies.