On February 23, 2021 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported publication of an electronic poster at the CAR-TCR Summit Europe 2021 with data from a preclinical study evaluating pelareorep and chimeric antigen receptor (CAR) T cell combination therapy in solid tumors (Press release, Oncolytics Biotech, FEB 23, 2021, View Source [SID1234575453]).
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Newly published results show that loading CAR T cells with pelareorep vastly improved their persistence and efficacy in a murine solid tumor model, in stark contrast to preclinical studies using intratumoral infection with the VSV oncolytic virus that weakened CAR T cells. Efficacy of pelareorep-loaded CAR T cell ("CAR/Pela") therapy was further enhanced by boosting mice 8 days later with a single intravenous dose of pelareorep ("pelareorep boost"), generating highly persistent CAR T cells, inhibition of recurrent tumor growth, and ultimately tumor cures. These synergistic immune effects were specific to pelareorep, as intravenous boosting with VSV did not augment CAR/Pela therapy or prevent the growth of recurrent tumors. Survival data from the preclinical study are shown below:
"These very exciting data demonstrate pelareorep’s ability to overcome major shortcomings of CAR T cells," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics Biotech Inc. "Despite commercial success in hematological cancers, CAR T therapies have limited efficacy against solid tumors due to immunosuppressive tumor microenvironments (TMEs) that promote T cell exhaustion and exclusion. Pelareorep’s ability to reverse immunosuppressive TMEs has been well documented in the clinic, and combining CAR T cells with pelareorep may enable their success against solid cancers. This would be a major advancement, as it would substantially broaden the applicability of CAR T cells to a variety of highly prevalent and difficult-to-treat indications."
Andrew de Guttadauro, President of Oncolytics Biotech U.S. and Global Head of Business Development, added, "While our primary focus is on advancing our lead breast cancer program to a registrational trial, we continue to evaluate additional opportunities to expand pelareorep’s business development and partnership potential. In clinical studies, pelareorep recruited high concentrations of T cells to solid tumors, positioning it to synergistically interact with checkpoint inhibitors. In this newly published study, we show the synergistic benefits of pelareorep can be extended to additional cutting-edge immunotherapeutic agents. Based on these findings, we are specifically exploring a partnership strategy to further the development of pelareorep as an enabling technology for CAR T cells and additional immunotherapies that require immune effector cell infiltration in solid tumors."
The electronic poster titled "Combination Therapy with Oncolytic Viruses and CAR T Cells," was developed in collaboration with researchers from the Mayo Clinic, Duke University, and Oncolytics. It is available on the Posters & Publications page of Oncolytics’ website (LINK).
About CAR T cells and CAR T therapy
The CAR T process begins when blood is drawn from a patient and their T cells are separated so they can be genetically engineered to produce chimeric antigen receptors (CARs). These receptors enable the T cells to recognize and attach to a specific protein or antigen on tumor cells. Once the engineering process is complete, a laboratory can increase the number of CAR T cells into the hundreds of millions. Finally, the CAR T cells will be infused back into the patient where, ideally, the engineered cells further multiply, and recognize and kill cancer cells. Historically, solid tumors have been considered beyond the reach of CAR T therapy due to their tumor microenvironment, which is detrimental to CAR T cell entry and activity, amongst other challenges.1
About Pelareorep
Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.