Scientists have developed a new type of cancer vaccine that shows promise in clearing out leukemia in mice. The technique involves reprogramming cancer cells into immune cells so that they can teach the immune system how to fight off the disease.
In a fair fight, our immune system would defeat cancer every time. But this dastardly disease doesn’t fight fair, instead using a range of underhanded tricks to evade detection. Immunotherapy is an emerging treatment that involves supercharging the immune system to better fight off cancer, with some very promising early results.
One of the most common forms of immunotherapy works by removing T cells from a patient, programming them to recognize specific cancer antigens, and setting them loose in the body to hunt down cancers with those antigens. The problem is, this requires a degree of guesswork in figuring out which antigens would be most useful for each patient.
So for the new study, scientists at Stanford Medicine developed a way to teach T cells to recognize a broader swathe of antigens, increasing the chances that a patient’s immune system would successfully attack their cancer. The trick is to convert cancer cells into macrophages, which are a type of antigen-presenting cell (APC) that teaches T cells what to look for.
“We hypothesized that maybe cancer cells reprogrammed into macrophage cells could stimulate T cells because those APCs carry all the antigens of the cancer cells they came from,” said Ravi Majeti, senior author of the study.
To test the idea, the researchers induced leukemia cells in mice to transform into APCs. And sure enough, the mice in the control group successfully cleared out their cancer. Better yet, the vaccine strategy seemed to work longer term to prevent the disease recurring.
“When we first saw the data showing clearance of the leukemia in the mice with working immune systems, we were blown away,” said Majeti. “We couldn’t believe it worked as well as it did. What’s more, we showed that the immune system remembered what these cells taught them. When we reintroduced cancer to these mice over 100 days after the initial tumor inoculation, they still had a strong immunological response that protected them.”
Next, the team tested the technique on mice with three different types of solid tumors – fibrosarcoma, breast cancer and bone cancer. The results weren’t quite as effective as in leukemia, but still showed positive effects.
And finally, the researchers experimented with cells taken from human patients. Sure enough, APCs derived from human leukemia cells seemed to be successful in teaching T cells from the same patient what to look for. That suggests that the method could eventually be applied to humans, but far more work still needs to be done.
“We showed that reprogrammed tumor cells could lead to a durable and systemic attack on the cancer in mice and a similar response with human patient immune cells,” said Majeti. “In the future we might be able to take out tumor cells, transform them into APCs and give them back to patients as a therapeutic cancer vaccine. Ultimately, we might be able to inject RNA into patients and transform enough cells to activate the immune system against cancer without having to take cells out first. That’s science fiction at this point, but that’s the direction we are interested in going.”
The research was published in the journal Cancer Discovery.
Source: Stanford Medicine
