Could hitting tumors with a virus before delivering anti-cancer treatments spur an immune reaction and boost treatment response? A new study says yes.
According to a study published in the journal Science Translational Medicine by Ludwig Cancer Research, using what is known as oncolytic virotherapy could dramatically improve response rates in patients receiving checkpoint blockade, a powerful strategy to harness the immune response to treat cancer
Oncolytic virotherapy is an investigational intervention that uses viruses to destroy tumors.
The study was lead by Dmitriy Zamarin, a member of Ludwig's Collaborative Laboratory at Memorial Sloan Kettering Cancer Center (MSK)along with James Allison of the MD Anderson Cancer Center in Houston, and Jedd Wolchok, Director of the Ludwig Collaborative Laboratory at MSK.
They evaluated a combination therapy in which the Newcastle disease virus (NDV), a bird virus not ordinarily harmful to humans, is injected straight into one of two melanoma tumors implanted in mice. Then an antibody was injected that releases the brakes on the immune response.
According to the researchers, this combination induced a "potent and systemically effective anti-tumor immune response" that was so overpowering it also killed the non-infected tumor, and later showed efficacy in killing cancer cells in tumor types that have thus far proven to be resistant to checkpoint blockade and other immunotherapeutic strategies.
"Many patients have benefited from cancer immunotherapies but they have not been effective for all patients, or against all cancer types, since most cancers can potently suppress immune responses," said Zamarin. "We want to extend the benefits of immunotherapies to more patients and optimize their use against a larger variety of cancers."
When they injected NDV, cancer-killing immune cells poured into the tumor. Surprisingly, they also poured into a distant tumor in which NDV was not even detected, suggesting very potent pre-treatment potential.
According to the team, it works because NDV infection alerts the immune system's T cells to cancerous cells, which would otherwise be able to hide.
Perhaps equally as exciting, it appears that this effect has some durability: when the same tumors were re-introduced into treated mice, an existing immune response quickly killed the tumors.
Next steps: Expand production of NDV and devise protocols to evaluate their combination therapy in early stage clinical trials.
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