A therapy developed by Yale researchers stimulates immune cells to shrink or kill tumors in mice, according to a new study published in Journal of Experimental Medicine. This therapy is effective alone or in combination with existing cancer immunotherapy, and appears to have long-lasting effects, the researchers said.
The research team, led by researchers Yale Akiko Iwasaki and Anna Pyle, examined whether synthetic RNA molecules developed to fight viruses can also trigger an immune response to tumors. The molecule, called Stem Loop RNA 14 (SLR14), is specifically designed to activate genes that detect viruses and other threats in cells.
"Our idea is to mimic viral infections in tumors, fool the immune system into thinking there is an infection and get rid of it," Iwasaki said.
To test this theory, researchers experimented with several different approaches. They injected SLR14 directly into tumors in mice and observed the destruction of cancer by strong immune system T cells. When they provide therapy to one site on the tumor, it also stimulates T cells to respond at different sites, showing a broad effect.
In another experiment, they mimicked cancer metastases by spreading tumor cells throughout the body by injecting them through the heart's left ventricle. The results show that SLR therapy in solid tumors can inhibit further growth of metastatic cancer.
Further investigation shows that SLR14 is comparable to existing cancer immunotherapy drugs, and can improve its anti-tumor response. "This has a significant effect as a single therapeutic agent, and when combined with current immune therapy, we see a synergistic effect," Iwasaki noted.
The researchers also found that the "memory" of the immune system was induced by therapy, protecting animals from recurrence. "We need to use the immune system, which has a long memory, to find tumors and kill them before they become cancerous. We show this long-term immunity after SLR injection," he said.
The next step in research is testing the therapy itself, and in combination with other therapies, in trials in humans.
Scientists help the immune system find hidden cancer cells
Xiaodong Jiang et al. Intratumoral delivery of RIG-I SLR14 agonists induces a strong antitumor response, Journal of Experimental Medicine (2019). DOI: 10.1084 / jem.20190801
Drugs show promise as immune therapy for cancer (2019, 15 October)
taken October 15, 2019
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