On September 29, 2026 Oncolytics Biotech Inc. (Nasdaq: ONCY) ("Oncolytics" or the "Company"), a clinical-stage immunotherapy company developing pelareorep, reported data published in the Proceedings of the National Academy of Sciences show pelareorep’s ability to change an immunologically inactive liver cancer tumor microenvironment into one that is immunologically active and potentially susceptible to immune-based therapy. The academic paper titled "MicroRNA-driven regulation of immunosuppressive microenvironment in hepatocellular carcinoma" was published in Proceedings of the National Academy of Sciences on September 28, 2026 (link to the paper). Pelareorep is an investigational, systemically active immunotherapy that promotes potentially protective immune responses, including the upregulation of key inflammatory cytokines resulting in the formation of tertiary lymphoid structures and the expansion of tumor-infiltrating lymphocytes.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"This publication provides additional evidence that pelareorep alters the tumor microenvironment in traditionally challenging indications," said Thomas Heineman, MD, PhD, Chief Medical Officer of Oncolytics. "The ability to enable chemotherapy, checkpoint inhibitors, RAS inhibitors, and other treatments to be viable in cancers that have previously been untreatable is helping to drive our business development conversations. While liver cancer is not an indication we intend to pursue at this time, the data align with our narrative that pelareorep works in challenging tumor types and can be considered a backbone immunotherapy that can improve the activity of many cancer treatments, while maintaining a favorable safety profile."
Hepatocellular carcinoma tends to have low levels of CD8+ T cell infiltration and Inducible T cell Costimulatory Ligand ("ICOSL") in addition to high levels of Transforming Growth Factor Beta / Suppressor of Cytokine Signaling 1 / Yes-associated protein 1, which are signs of a significantly immunosuppressive tumor microenvironment. Preclinical data presented in this publication show that infection with pelareorep reversed several of these effects, including dramatic increases in PD-L1 expression, ICOSL levels on tumor cells, and CD8+ T cell density. These changes imply the tumor microenvironment shifted from immunologically inactive or "cold" to "hot" or immunologically active, enabling immune-mediated lysis of tumor cells.
This cascade of immune responses creates an environment in which checkpoint inhibitors and other therapies can be effective. Pelareorep has previously shown the ability to initiate coordinated changes in the tumor microenvironment, including the formation of tertiary lymphoid structures, that are associated with improved responses to immunotherapy. In this paper, there is a noted increase in CD8+ T cells, PD-1/PD-L1 upregulation, and Inducible T cell Co-stimulator-ICOSL signaling. These are all necessary conditions for immunotherapies like checkpoint inhibitors to work in liver cancer, which is an especially challenging tumor type.
About Pelareorep
Pelareorep is an intravenously delivered, systemically active, investigational immunotherapy with a dual mechanism of action that selectively replicates in tumor cells while activating both innate and adaptive anti-tumor immune responses, including the upregulation of key inflammatory cytokines resulting in the formation of tertiary lymphoid structures and the expansion of tumor-infiltrating lymphocytes. It has been administered to over 1,200 patients, and clinical studies have demonstrated pelareorep’s potential to enhance the activity of checkpoint inhibitors and other anti-cancer therapies across multiple solid tumor types.
(Press release, Oncolytics Biotech, SEP 29, 2026, View Source [SID1234671175])