RE:RE:RE:RE:CD8+ TiLs and T-cell exhaustionPelareorep driven blood TIL expansion in patients with pancreatic, breast and colon cancer.
Identification of TIL clones was performed by immunosequencing of the CDR3 regions of human T-cell receptor-b (TCRb) chains (ImmunoSEQ Assay, Adaptive Biotechnologies). DNA was isolated from tissue and blood at baseline and from blood collected posttreatment. TCRb CDR3 regions were amplified by a multiplex, bias-controlled PCR with primers targeting the V and J genes of T cells as well as primers targeting housekeeping genes to quantitate the total nucleated cells in each sample. PCR products were sequenced on an Illumina NextSeq.
[ Clonal T cell expansion (which pelareorep is capable of achieving) is the process of T cell activation and proliferation which occurs naturally in vivo when the human body is actively fighting an infection or an immune system attack.]
Results: Pela treatment 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. We also observed that pre-existing TIL clonal expansion in the blood seemed to correlate with reductions in tumor volume in pancreatic cancer and to a lesser extent in CRC patients who received multiple cycles of therapy. Interestingly, unlike atezolizumab, pela’s clinical activity was lost when combined with avelumab, a PD-LI inhibitor capable of binding Fc receptors and inducing ADCC. The addition of avelumab eliminated pre-existing TIL expansion in the blood highlighting the importance of TIL expansion following pela therapy.
"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."