Stanford Medicine researchers have succeeded in transforming cancer cells into immune cells, which are capable of teaching the body's immune system to fight the same cancer cells from and attack them.
"This approach could open up a whole new therapeutic pathway to treat cancer," said Dr. Ravi Majeti, Professor of Hematology and lead author of the study published March 1 in Cancer Discovery.
Some of the most promising cancer treatments use the patient's own immune system to attack the disease, often by slowing down immune responses to cancer or by teaching the immune system to recognize and attack cancer more vigorously.
And it is that T cells, part of the immune system that learns to identify and attack new pathogens such as viruses, can be trained to recognize specific cancer antigens, which are proteins that generate an immune response.
Therefore, it would be better to train T cells to recognize cancer through processes that more closely mimic the way things naturally occur in the body—such as the way a vaccine teaches the immune system to recognize cancer. pathogens?.
T cells learn to recognize pathogens because antigen presenting cells ?APC? Special cells gather bits of the pathogen and show them to T cells in a way that tells them, "This is what the pathogen looks like, go get it."
Something similar in cancer would be for APCs to take up the many antigens that characterize a cancer cell. Thus, instead of T cells being programmed to attack one or a few antigens, they would be trained to recognize many cancer antigens and would be more likely to mount a multiple attack on cancer.
Now that researchers have become adept at turning one type of cell into another, Majeti and his colleagues had a hunch that if they turned cancer cells into a type of APC called macrophages, they would naturally be adept at teaching T cells what to do. attack.
"Our hypothesis was that maybe cancer cells reprogrammed into macrophages could stimulate T cells because those APCs carry all the antigens of the cancer cells they came from," explained Majeti, who is also director of the Institute for Stem Cell Biology. and Regenerative Medicine and director of the Ludwig Center for Cancer Stem Cell Medicine and Research.
The study builds on previous research from Majeti's lab showing that cells taken from patients with one type of acute leukemia could become non-leukemic macrophages with many of the properties of APCs.
In the current study, the researchers programmed mouse leukemia cells to induce some of them to transform into APCs. When they tested their cancer vaccine strategy on the mouse immune system, the mice successfully killed the cancer.
"When we first saw the data showing clearance of leukemia in mice with functioning immune systems, we were amazed," Majeti said. "We couldn't believe it worked so well."
Other experiments showed that cells created from cancer cells acted as antigen-presenting cells that sensitized T cells to cancer.
"What's more, we showed that the immune system remembered what these cells had taught them," says Majeti. "When we reintroduced the cancer into these mice more than 100 days after the initial tumor inoculation, they still had a strong immune response that protected them."
"We asked ourselves: if this works for leukemias, will it also work for solid tumors?" Majeti said. The team tested the same approach with mouse fibrosarcoma, breast cancer, and bone cancer.
"The transformation of cancer cells from solid tumors was not as effective, but we still saw positive results," Majeti said. With all three types of cancer, the creation of tumor-derived APCs led to a significant improvement in survival.
Finally, the researchers returned to the original type of acute leukemia. When APCs derived from human leukemia cells were exposed to human T cells from the same patient, they observed all the signs one would expect if the APCs were actually teaching the T cells to attack leukemia.
"We showed that the reprogrammed tumor cells could cause a long-lasting, systemic attack on cancer in mice and a similar response with immune cells from human patients," Majeti said. "In the future we might be able to extract tumor cells, transform them into APCs, and return them 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 extract cells first," Majeti said. "That's science fiction right now, but that's the direction we're interested in moving in."
With information from Stanford Medicine
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