White blood cells from a unique breed of cancer-resistant mice have cured advanced cancers in normal mice, researchers report. When injected the immune cells sought out and killed existing tumours and also protected the mice against lethal doses of new, highly aggressive cancers.
The “resistant-cell therapy” appears to work without toxic side effects, and the researchers hope that a greater understanding of the mechanism may enable the technique to be used in humans in the future.
The researchers extracted the white blood cells from a lineage of mice with a genetic mutation that enables their immune systems to fight off cancer. These cancer-resistant mice all descend from a single mouse with this mutation that the team discovered in their lab in 1999.
“To find an animal that was resistant to this aggressive cancer was unprecedented, because it’s such a nasty tumour,” says Mark Willingham, who carried out the research with colleagues at Wake Forest University School of Medicine, US.
The white blood cells were injected into normal mice with advanced tumours. The team found that the tumours quickly disappeared and the mice continued to be resistant to new cancers that arose up to 10 months later. The mice showed no ill effects from the treatment, the scientists say, and even killed a highly aggressive kind of tumour that had never been defeated before by any therapy.
The researchers believe that the mutation is caused by a single dominant gene, because of its pattern of inheritance in mice.
“That gives us hope that there’s one simple switch that you can throw somewhere in the signalling pathway to turn on this tumour-fighting behaviour,” Willingham says. He suggests that drugs could eventually be designed to target that switch.
However, the gene has not yet been identified. The researchers suspect this is because it is mobile – moving from one chromosome to another. The same mutation has not been found in unrelated mice, but Willingham suspects other cancer-resistant lineages exist.
“It’s possible that this trait in humans is even better,” says Zheng Cui, who led the study. Defences against cancer are much more robust in humans than in mice, Cui notes, because humans must live much longer before they can reproduce.
The anticancer components of the white blood cells in the mutated mice appear to be ordinary “immune moppers” – macrophages, neutrophils and natural killer cells – rather than T cells. This is significant, because while T cells must have previously been exposed to a pathogen in order to attack it, immune moppers have an innate response to engulf and kill the cancer.
Some forms of cancer therapy in humans use immune compounds such as interleukin-2 to boost the tumour-killing activity of white blood cells, but unfortunately these therapies usually have toxic side-effects. “The big message of this mouse is not so much that it’s rejecting the cancer cells but that it’s not harming the mouse,” says Willingham. “I think there are a lot of hurdles to go over, but there is a lot of exciting stuff in this [research],” says Walter Quan, director of cancer immunotherapy at East Carolina University, US, who was not involved in this study.