RE:RE:RE:RE:RE:CD8+ TiLs and T-cell exhaustion Many tumors prevent stem-like T cells from generating cytotoxic T cells in the tumor that could attack the cancer.
Current immunotherapies aim to prevent the cancer from switching off immune responses at a later phase that cause T cell exhaustion. Checkpoint inhibitor therapies, for example, aim to release the blockade of fully differentiated cytotoxic T cells and "switch them back on". Before the dreaded T cell exhaustion sets in, which other researchers are trying to prevent, differentiated T cells must also be present.
In ONCY's recently reported Tils work, pelareorep was observed to increase the expansion of pre-existing and new TIL clones in the blood in from all tumor samples after one cycle of treatment. ONCY also observed that pre-existing TIL clonal expansion in the blood seemed to correlate with reductions in tumor volume in pancreatic cancer which appears to confirm the Mahalingham et al (2019) Phase 1b clinical study in pancreatic cancer (PDAC) involving the checkpoint inhibitor pembrolizumab + pelareorep.
Mahalingham found that "while clonal expansion was more pronounced after pembrolizumab, it was the early clonal expansion achieved with pelareorep priming as well as the durable clonal expansion that appeared to be associated with improved long-term outcomes. To our knowledge, these results are unique in terms of identifying the significance of the immune priming effect of immune adjuncts in PDAC and the maintenance of this effect by ICIs."
Mahalingham went on to say that "Similar to our study, research by Hopkins et al. found that PDAC patients treated with nivolumab and a Listeria monocytogenes bacteria expressing mesothelin experience an increase in clonal diversity in peripheral T cells after thee cycles of treatment . Importantly, Hopkins et al. also found that LTS (OS > 6 months) have higher levels of peripheral T cell clonality post-treatment relative to STS (OS < 6 months). Thus, peripheral T cell clonality may by an important biomarker for checkpoint blockade therapy administered in combination with immune priming agents such as oncolytic viruses or cancer vaccines."
And as reported in ONCY's ASCO 2024 poster entitled: " Pelareorep driven blood TIL expansion in patients with pancreatic, breast and colon cancer " ...
"Accordingly, pela therapy may offer a means to directly expand TILs without the need for tumor resection, ex vivo TIL expansion, T cell ablation and IL-2 therapy."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942612/