RE:RE:G12D/G12V KRAS mutation in PC & CRC patients respond to PelaDecember 15, 2023 -
Translational Relevance
Pelareorep (PELA) is an oncolytic virus formulation that is currently being investigated for multiple myeloma therapy. Our study shows that combination PELA, bortezomib, and dexamethasone therapy is safe, well-tolerated, and induces an inflammatory response in patients with multiple myeloma characterized by significant T and natural killer cell activation, enhanced chemokine release, bone marrow T-cell infiltration, and increased programmed death-ligand 1 expression in multiple myeloma cells. Multiplexed immune cell profiling of the tumor immune microenvironment (TiME) defined a novel immune-primed multiple myeloma phenotype (CD138+IDO1+HLA-ABCHigh) and revealed increased interactions between multiple myeloma and immune cell subsets in bone marrow from responders compared with nonresponders. Our findings support further investigation of oncolytic virotherapy-driven immune reprogramming as a potential strategy for sensitizing immunologically “cold” tumors to immune checkpoint inhibitor therapies. Additionally, our study demonstrates that TiME immune cell profiling should be explored as a potential clinical tool to distinguish early responders and nonresponders.
https://aacrjournals.org/clincancerres/article/29/24/5012/731670/Facts-and-Hopes-on-RAS-Inhibitors-and-Cancer