Nanoparticles reprogram immune cells to fight cancer
Nanoparticles reprogram immune cells to fight cancer
Researchers at Fred Hutchinson Cancer Research Center have developed biodegradable nanoparticles that can be used to genetically program immune cells to recognize and demolish cancer cells—while the immune cells are still inwards the figure.
In a proof-of-principle examine to be published April seventeen in Nature Nanotechnology, the team displayed that nanoparticle-programmed immune cells, known as T cells, can rapidly clear or slow the progression of leukemia in a mouse model.
“Our technology is the very first that we know of to quickly program tumor-recognizing capabilities into T cells without extracting them for laboratory manipulation,” said Fred Hutch’s Dr. Matthias Stephan, the probe’s senior author. “The reprogrammed cells begin to work within twenty four to forty eight hours and proceed to produce these receptors for weeks. This suggests that our technology has the potential to permit the immune system to quickly climb on a strong enough response to demolish cancerous cells before the disease becomes fatal.”
Cellular immunotherapies have shown promise in clinical trials, but challenges remain to making them more widely available and to being able to deploy them quickly. At present, it typically takes a duo of weeks to prepare these treatments: the T cells must be eliminated from the patient and genetically engineered and grown in special cell processing facilities before they are infused back into the patient. These fresh nanoparticles could eliminate the need for such expensive and time consuming steps.
Albeit his T-cell programming method is still several steps away from the clinic, Stephan imagines a future in which nanoparticles convert cell-based immunotherapies—whether for cancer or infectious disease—into an lightly administered, off-the-shelf treatment that’s available anywhere.
“I’ve never had cancer, but if I did get a cancer diagnosis I would want to begin 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.”
The figure as a genetic engineering lab
Stephan created his T-cell homing nanoparticles as a way to bring the power of cellular cancer immunotherapy to more people.
In his method, the laborious, time-consuming T-cell programming steps all take place within the figure, creating a potential army of “serial killers” within days.
As reported in the fresh probe, Stephan and his team developed biodegradable nanoparticles that turned T cells into CAR T cells, a particular type of cellular immunotherapy that has delivered promising results against leukemia in clinical trials.
The researchers designed the nanoparticles to carry genes that encode for chimeric antigen receptors, or CARs, that target and eliminate cancer. They also tagged the nanoparticles with molecules that make them stick like burrs to T cells, which absorb the nanoparticles. The cell’s internal traffic system then directs the nanoparticle to the nucleus, and it dissolves.
The investigate provides proof-of-principle that the nanoparticles can educate the immune system to target cancer cells. Stephan and his team designed the fresh CAR genes to integrate into chromosomes housed in the nucleus, making it possible for T cells to begin decoding the fresh genes and producing CARs within just one or two days.
Once the team determined that their CAR-carrying nanoparticles reprogrammed a noticeable percent of T cells, they tested their efficacy. Using a preclinical mouse model of leukemia, Stephan and his colleagues compared their nanoparticle-programming strategy against chemotherapy followed by an infusion of T cells programmed in the lab to express CARs, which mimics current CAR-T-cell therapy.
The nanoparticle-programmed CAR-T cells held their own against the infused CAR-T cells. Treatment with nanoparticles or infused CAR-T cells improved survival fifty eight days on average, up from a median survival of about two weeks.
The investigate was funded by Fred Hutch’s Immunotherapy Initiative, the Leukemia & Lymphoma Society, the Phi Beta Psi Sorority, the National Science Foundation and the National Cancer Institute.
Next steps and other applications
Stephan’s nanoparticles still have to clear several hurdles before they get close to human trials. He’s pursuing fresh strategies to make the gene-delivery-and-expression system safe in people and working with companies that have the capacity to produce clinical-grade nanoparticles. Additionally, Stephan has turned his glances to treating solid tumors and is collaborating to this end with several research groups at Fred Hutch.
And, he said, immunotherapy may be just the beginning. In theory, nanoparticles could be modified to serve the needs of patients whose immune systems need a boost, but who cannot wait for several months for a conventional vaccine to kick in.
“We hope that this can be used for infectious diseases like hepatitis or HIV,” Stephan said. This method may be a way to “provide patients with receptors they don’t have in their own bod,” he explained. “You just need a little number of programmed T cells to protect against a virus.”
More information: In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers, Nature Nanotechnology (2017). nature.com/articles/doi:Ten.1038/nnano.2017.57
Provided by: Fred Hutchinson Cancer Research Center
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Nanoparticles reprogram immune cells to fight cancer
Nanoparticles reprogram immune cells to fight cancer
Researchers at Fred Hutchinson Cancer Research Center have developed biodegradable nanoparticles that can be used to genetically program immune cells to recognize and demolish cancer cells—while the immune cells are still inwards the assets.
In a proof-of-principle explore to be published April seventeen in Nature Nanotechnology, the team demonstrated that nanoparticle-programmed immune cells, known as T cells, can rapidly clear or slow the progression of leukemia in a mouse model.
“Our technology is the very first that we know of to quickly program tumor-recognizing capabilities into T cells without extracting them for laboratory manipulation,” said Fred Hutch’s Dr. Matthias Stephan, the probe’s senior author. “The reprogrammed cells begin to work within twenty four to forty eight hours and proceed to produce these receptors for weeks. This suggests that our technology has the potential to permit the immune system to quickly climb on a strong enough response to demolish cancerous cells before the disease becomes fatal.”
Cellular immunotherapies have shown promise in clinical trials, but challenges remain to making them more widely available and to being able to deploy them quickly. At present, it typically takes a duo of weeks to prepare these treatments: the T cells must be eliminated from the patient and genetically engineered and grown in special cell processing facilities before they are infused back into the patient. These fresh nanoparticles could eliminate the need for such expensive and time consuming steps.
Albeit his T-cell programming method is still several steps away from the clinic, Stephan imagines a future in which nanoparticles convert cell-based immunotherapies—whether for cancer or infectious disease—into an lightly administered, off-the-shelf treatment that’s available anywhere.
“I’ve never had cancer, but if I did get a cancer diagnosis I would want to commence 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.”
The figure as a genetic engineering lab
Stephan created his T-cell homing nanoparticles as a way to bring the power of cellular cancer immunotherapy to more people.
In his method, the laborious, time-consuming T-cell programming steps all take place within the assets, creating a potential army of “serial killers” within days.
As reported in the fresh investigate, Stephan and his team developed biodegradable nanoparticles that turned T cells into CAR T cells, a particular type of cellular immunotherapy that has delivered promising results against leukemia in clinical trials.
The researchers designed the nanoparticles to carry genes that encode for chimeric antigen receptors, or CARs, that target and eliminate cancer. They also tagged the nanoparticles with molecules that make them stick like burrs to T cells, which absorb the nanoparticles. The cell’s internal traffic system then directs the nanoparticle to the nucleus, and it dissolves.
The investigate provides proof-of-principle that the nanoparticles can educate the immune system to target cancer cells. Stephan and his team designed the fresh CAR genes to integrate into chromosomes housed in the nucleus, making it possible for T cells to begin decoding the fresh genes and producing CARs within just one or two days.
Once the team determined that their CAR-carrying nanoparticles reprogrammed a noticeable percent of T cells, they tested their efficacy. Using a preclinical mouse model of leukemia, Stephan and his colleagues compared their nanoparticle-programming strategy against chemotherapy followed by an infusion of T cells programmed in the lab to express CARs, which mimics current CAR-T-cell therapy.
The nanoparticle-programmed CAR-T cells held their own against the infused CAR-T cells. Treatment with nanoparticles or infused CAR-T cells improved survival fifty eight days on average, up from a median survival of about two weeks.
The explore was funded by Fred Hutch’s Immunotherapy Initiative, the Leukemia & Lymphoma Society, the Phi Beta Psi Sorority, the National Science Foundation and the National Cancer Institute.
Next steps and other applications
Stephan’s nanoparticles still have to clear several hurdles before they get close to human trials. He’s pursuing fresh strategies to make the gene-delivery-and-expression system safe in people and working with companies that have the capacity to produce clinical-grade nanoparticles. Additionally, Stephan has turned his glances to treating solid tumors and is collaborating to this end with several research groups at Fred Hutch.
And, he said, immunotherapy may be just the beginning. In theory, nanoparticles could be modified to serve the needs of patients whose immune systems need a boost, but who cannot wait for several months for a conventional vaccine to kick in.
“We hope that this can be used for infectious diseases like hepatitis or HIV,” Stephan said. This method may be a way to “provide patients with receptors they don’t have in their own assets,” he explained. “You just need a lil’ number of programmed T cells to protect against a virus.”
More information: In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers, Nature Nanotechnology (2017). nature.com/articles/doi:Ten.1038/nnano.2017.57
Provided by: Fred Hutchinson Cancer Research Center
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A fresh discovery by researchers at the Fred Hutchinson Cancer Research Center in Seattle makes an significant step in identifying which specific T cells within the diverse army of a person’s immune system are best suited to .
Immunotherapy shows promise in preventing leukemia relapse
Fred Hutchinson Cancer Research Center announced promising results from an early trial in which patients with high-risk acute myeloid leukemia received genetically engineered immune cells. Of the twelve AML patients who received .
Stan Riddell, Fred Hutch cancer immunotherapy innovator, to present at AAAS Annual Meeting
Dr. Stanley Riddell, an immunotherapy researcher and oncologist at Seattle’s Fred Hutchinson Cancer Research Center, on Feb. Fourteen will present an update on fresh adoptive T-cell strategies for cancer at the annual meeting of .
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Stanford researchers accidentally discovered that metal nanoparticles invented for anemia treatment have another use: triggering the immune system’s capability to ruin tumor cells.
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Cancer treatments that mobilize the bod’s immune system to fight the disease have generated a lot of excitement in the past few years. One form of immunotherapy called checkpoint blockade is especially promising. But while .