Oncolytic Virus, CAR T Combination Preclinical Study Shows Activity in Solid Tumors

Loading chimeric antigen receptor (CAR) T-cells with the oncolytic virus pelareorep improved their efficacy in solid tumor mouse models in a preclinical study presented at the CAR-TCR Summit Europe 2021.¹

CAR T-cells have made waves in blood cancer treatment, with 3 options currently FDA approved to treat lymphomas (axicabtagene ciloleucel, brexucabtagene autoleucel, and lisocabtagene maraleucel) and 1 approved for both B-cell precursor acute lymphoblastic leukemia and large B-cell lymphoma (tisagenlecleucel). But the progress has not been paralleled in solid tumors, which are typically resistant to the treatment.

Oncolytic viruses, which target cancer cells for infection and destruction, have shown promise as primers that can make hard-to-treat solid tumors vulnerable to therapies like immune checkpoint inhibitors and CAR T-cells.^2,3 The newly published results, a product of collaboration between Mayo Clinic, Duke University, and Oncolytics Biotech, are good news in an area where progress has been slow so far.⁴

"These very exciting data demonstrate pelareorep's ability to overcome major shortcomings of CAR T-cells," Matt Coffey, MD, president and chief executive officer of Oncolytics Biotech, Inc., said in a statement. "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."

Study investigators found that loading the CAR T-cells with pelareorep increased the efficacy of the treatment in mouse models, and that boosting the mice with intravenous pelareorep 8 days later further improved outcomes. The combination treatment plus booster generated persistent CAR T-cells, inhibited recurrent tumor growth, and cured tumors in those mice. Notably, the same result was not seen when researchers loaded CAR T-cells with a different oncolytic virus called VSV. Instead, VSV weakened the CAR T-cells.

Andrew de Guttadauro, president of Oncolytics Biotech US and global head of business development, sees potential for pelareorep in multiple cancer types.

"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,” Guttadauro said. “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."

References

1. Oncolytics Biotech reports preclinical data demonstrating the synergistic anti-cancer activity of pelareorep combined with CAR T cell therapy in solid tumors. News release. Oncolytics Biotech, Inc; February 23, 2021. Accessed February 24, 2021. https://www.oncolyticsbiotech.com/press-releases/detail/527/oncolytics-biotech-reports-preclinical-data-demonstrating

2. McNulty R. Oncolytic virus shows promise in colon cancer treatment. Am J Manag Care. Published online December 1, 2020. https://www.ajmc.com/view/oncolytic-virus-shows-promise-in-colon-cancer-treatment

3. AJMC Staff. Scientists hopeful about early study combining oncolytic virus, CAR T. Am J Manag Care. Published online September 4, 2020. https://www.ajmc.com/view/scientists-hopeful-about-early-study-combining-oncolytic-virus-car-t

4. Kottke T, Evgin L, Vloten J, et al. Combination therapy with oncolytic viruses and CAR T cells. Presented at: CAR-TCR Summit Europe 2021; February 16-18.