Researchers at the Fred Hutchinson Cancer Researcher Center have reportedly engineered biodegradable nanoparticles that can genetically reprogram immune cells to recognize and destroy cancer cells, without taking the immune cells out to manipulate them.
The team demonstrated their idea in a proof-of-principle study published in Nature Nanotechnology. They showed that reprogrammed immune cells, or T cells, help to slow the progression of leukemia in a mouse model.
“Our technology is the 1st that we know of to quickly program tumor-recognizing capabilities into T cells without extracting them for laboratory manipulation,” senior author Matthias Stephan said in prepared remarks. “The reprogrammed cells begin to work within 24 to 48 hours and continue to produce these receptors for weeks. This suggests that our technology has the potential to allow the immune system to quickly mount a strong enough response to destroy cancerous cells before the disease becomes fatal.”
Current cellular immunotherapies require weeks of preparation. T cells are removed from the patient, genetically engineered and grown in cell processing facilities before they are infused back into the patient. Stephan said the team hopes their nanoparticles could eliminate those expensive and time-consuming steps.
“I’ve never had cancer, but if I did get a cancer diagnosis I would want to start treatment right away,” Stephan said. “I want to make cellular immunotherapy a treatment option the day of diagnosis and have it able to be done in an outpatient setting near where people live.”
Stephan and his team engineered biodegradable nanoparticles that turn T cells into CAR T cells, a cell therapy that has shown promise in early clinical trials as a treatment for leukemia.
The nanoparticles carry genes that encode for chimeric antigen receptors, or CARs, that target and destroy cancer, Stephan said. They also tagged the nanoparticles with molecules that help them stick to T cells, which engulf and dissolve the nanoparticle.
The CAR genes integrate into chromosomes of T cells, which begin decoding the new genes and producing CARs within 1 or 2 days, according to the team.
The researchers used a preclinical mouse model of leukemia and compared their nanoparticle-programming strategy against chemotherapy followed by an infusion of T cells programmed in the lab to express CARs. They found that treatment with nanoparticles or infused CAR-T cells improved surivival 58 days on average.
Stephan’s nanoparticle technique has a long way to go before human clinical trials. In the meantime, he hopes to work with companies that can produce clinical-grade nanoparticles while exploring new ways to make the gene-delivery-and-expression system safe in people. Stephan said he is focusing on treating solid tumors.