RE:RE:RE:CD8+ TiLs and T-cell exhaustionIn February 2024 the FDA approved Iovance Biotreherapeutics' TiLs therapy, via the FDA's Accelerated Approval process, for the treatment of advanced melanoma cancer which bodes well for ONCY's drug platform pelareorep, in the treatment of multiple cancers that currently are Orphan/Rare cancers or those cancers with "unmet treatment needs" such as advanced/metastatic breast cancer.
CD8+ TiL cells are critical mediators of cytotoxic effector function in cancer, however, in cancer, CD8+ TiL cells undergo a progressive loss of cytokine production and cytotoxicity, a state termed T-cell exhaustion as well as T-cell dysfuntion, resulting in a failure of T-cells to eradicate tumor cells in the tumor microenvironment (TME).
Also, high levels of PD-1 expression contribute to the characteristic dysfunction seen in exhausted CD8+ TiL cells. Correspondingly, in human tumors, a higher proportion of progenitor exhausted cells was associated with a greater likelihood of response to checkpoint blockade. While PD-1 blockade therapies have been successful in multiple tumor types, their effectiveness has been limited to between 10-20% of the patients treated.
Results from ONCY's AWARE-1 study showed that pelareorep treatment upregulated tumor PD-L1 expression, induced the generation and expansion of T cell clones, promoted tumor infiltration of CD8+ TiL cells, and increased the CelTIL score, a measure of tumor cellularity and inflammation associated with favorable clinical outcomes. Besides being able to overcome an immunosuppressive TME, pelareorp is a critical 'facilitator' in 'priming' the adaptive immune system in advance of PD-1 blockade, thus turning a 'cold' tumor into a 'hot' tumor that is more much conducive for PD-1 blockade, and a more effective I/O therapy than either agent alone.
https://www.newswire.ca/news-releases/oncolytics-biotech-r-and-solti-achieve-primary-endpoint-in-aware-1-study-871181269.html