April 13, 2022 - Empowering CAR-T cells to fight solid tumors by loading them with cancer-killing viruses.
Scientists are exploring various methods to enable CAR-T cell therapy to treat solid tumors. A research team at Mayo Clinic has now proposed loading engineered CAR-T cells with cancer-killing viruses as a promising approach. The findings show that systemic delivery of CAR-T cell therapy paired with an oncolytic virus warrant further development, the Mayo Clinic team said. The reovirus used in the study came from Oncolytics Biotech. The Canadian company is developing a reovirus candidate called pelareorep in combination with various agents in cancer, with HR-positive, HER2-negative breast cancer its most advanced clinical program.
CAR-T cell therapy has revolutionized treatment for certain blood cancers, but its use in solid tumors has been hampered. This is partly because the tumor microenvironment can be difficult for CAR-T cells to penetrate and survive. To overcome the challenge, the Mayo Clinic team originally tried pretreating mice with oncolytic viruses, but the immune response induced that way caused death among the following CAR-T cells.
The team then turned to a co-administration approach. The method could enable systemic delivery, expand CAR-T cells by stimulating their native T-cell receptors against viral antigens, and trigger other changes to further enhance the cells’ antitumor potency, the researchers argue.
When adding Oncolytics Biotech’s reovirus to the CAR-T cells the strategy of preloading with reovirus and subsequent boosting with the same virus also cured over 80% of mice of aggressive EGFRvIII brain tumors, “indicating that this strategy is not dependent on the location of the tumor being treated,” the researchers wrote in the study.
This new strategy also holds an advantage in that it doesn’t require lymphodepletion, the team noted.
And being able to deliver the therapy systemically represents another advantage over other approaches that require injection into the tumor because it would allow for treating patients with metastatic disease, Vile said.
https://www.fiercebiotech.com/research/loading-car-t-cells-cancer-killing-viruses-fight-solid-tumors