RE:RE:RE:RE:FDA comments on biomarkers as surrogate endpoints for AA
The journey of tumor-infiltrating lymphocytes (TiLs) as a biomarker in breast cancer: clinical utility in an era of checkpoint inhibition
Highlights
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TILs is a strong prognostic biomarker in some breast cancer subtypes in early-stage setting.
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Our method of quantifying TIL published 5+ years ago has been standardized, is reproducible, and has been adopted worldwide.
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TIL quantity has shown to be predictive of benefit from agents targeting PD-1/PD-L1 in the metastatic setting.
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TIL quantity correlates with many other immune biomarkers. TIL and PD-L1 expression together can identify ‘immune-rich’ tumors.
In Brief: [ONCY has developed predictive and prognostic biomarkers that can identify tumors with PD-L1 deficient expression (cold tumors) which are targets for pelareorep therapy (predictive biomarkers) and then monitor the effectiveness of treatment with pelareorep (prognostic biomarkers). Intravenous infusion of pelareorep results in pelareorep specifically targeting and infecting those "cold" cancer cells, causing the cell to express PD-L1 target sites on the cell surface, and turning the cancer into a "hot" tumor. In the process the innate immune system is stimulated and recognizes the "hot" tumor which effectively become "immune-rich" tumors with the production of NK and T-cells (TiLs) that together begin attacking the cancer cell. Accordingly, the hypoxic tumor microenvironment (TME) becomes remodeled through a complex immune resonse, and is converted into an environment that is receptive for the addition of PD-L1 immune checkpoint inhibitors. The consequence is that the I/O combination of pelareorep + PD-L1 immune checkpoint inhibitor becomes synergistic and more effective in killing the cancer than either I/O agent used as a monotherapy. And as this I/O combination is administered over time, the effectiveness of the therapy can be meaured by the use of ONCY's prognostic biomarker.]
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Investigating the relevant immune subsets important for prognosis and immunotherapy response is ongoing.
https://www.sciencedirect.com/science/article/pii/S0923753421021852