Cancer is fast becoming the leading cause of death in many countries, and that’s largely due to its ability to evade the attention of the immune system. One of the most promising types of treatment involves finding ways to boost the immune system’s response to the presence of cancer, and now two new mouse studies out of Yale University are reporting breakthroughs in this area.
The human immune system is an incredibly powerful tool, keeping constant watch over the entire body for anything that might cause trouble. But cancer is crafty, and uses a range of techniques to hide from the ever-vigilant T cells, the foot soldiers of the immune system.
Finding ways to help the immune system in this quest has shown great promise as a potential treatment for many kinds of cancers. Immunotherapy often involves removing a sample of a patient’s T cells, engineering them to target cancer and then reintroducing them into the body. Other studies have shown that it might be possible to do so within the body, like a vaccine. The overall technique is promising enough that it earned two scientists the 2018 Nobel Prize in Medicine for immunotherapy breakthroughs they made in the 1990s.
And now teams at Yale has reported new success in two separate mouse studies. In the first, researchers tested whether a molecule called Stem Loop RNA 14 (SLR14) could draw the attention of the immune system. SLR14 had previously been developed to fight off viruses, by activating genes that detect them and alert the immune system to their presence. In this case, the Yale team wanted to investigate whether the same mechanism would work against cancer.
“Our idea is to mimic a viral infection inside the tumor, tricking the immune system into thinking there is an infection and getting rid of it,” says Akiko Iwasaki, co-lead author of the study.
And sure enough, it seemed to work in a few different types of tests. The team injected the molecule directly into tumors in mice, and the animals’ T cells managed to destroy the cancer. They also found that delivering the therapy to one site on a tumor caused the T cells to respond to other areas too. In the third experiment, the researchers spread tumor cells throughout the animals’ bloodstreams to mimic metastasis – and the SLR14 therapy was still able to clean it up.
Better still, the researchers found that the immune system kept a kind of memory of the cancer, preventing it from reappearing down the track.
“We need to employ the immune system, which has a long memory, to find tumors and kill them before they become cancerous,” says Iwasaki. “We show this long-term immunity after injection of SLR.”
In the second study, another team of Yale researchers tested out a different form of cancer immunotherapy, using a new version of the CRISPR gene-editing tool. Normally CRISPR is used to precisely cut out problematic genes and/or insert new useful ones, but in this case the team used it to find genes associated with cancer, wherever they were hiding.
The new system is called Multiplexed Activation of Endogenous Genes as Immunotherapy (MAEGI). It works by searching the body for tens of thousands of different cancer-related genes, then marks their location and calls the immune system’s attention to them.
“This is an entirely new form of immunotherapy,” says Sidi Chen, senior author of the study. “And once those cells are identified, the immune system immediately recognizes them if they show up in the future.”
In tests on mice, the researchers found that MAEGI was effective against melanoma and triple-negative breast and pancreatic tumors. The technique either reduced or eliminated the cancers, even hunting down those located far away from the primary tumor.
With both techniques showing promise in cancer immunotherapy, the two teams are now working towards clinical trials in humans.
The SLR14 study was published in the Journal of Experimental Medicine, while the MAEGI study was published in Nature Immunology.
