Nature: Amazing! The Thin Metal Membrane Delivers Car-t Cells Efficiently Into Solid Tumors

- Jan 03, 2020-

What if a metal already used to repair fractures, straighten teeth and prevent clogged arteries could also be used to stop cancer from spreading?

In a new study, researchers from the Fred hutchinson cancer research center in the United States have found for the first time that a small, thin metal mesh loaded with cancer-fighting immune cells can shrink a preclinical model of ovarian cancer. The results were recently published in Nature Biomedical Engineering under the title "Nitinol thin films functionalized with car-t cells for the treatment of solid tumours."


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Pictures from Fred Hutchinson Cancer Research Center

Matthias Stephan, Ph.D., a researcher at the Fred hutchinson cancer research center and corresponding author of the paper, said, "cell therapies to fight cancer have been very successful in blood cancers, but not in solid tumors. Our findings show that thin metal mesh loaded with genetically engineered t-cells to fight ovarian cancer can remove tumors in 70 percent of treated mice, giving us an important step toward making cell therapy effective against solid tumors."

Solid tumors, including breast, ovarian and pancreatic cancer, have a variety of strategies to evade and fight back against immune cells that kill cancer, such as T cells, or car-t cells, that express chimeric antigen receptor (CAR).Injecting cancer-fighting cells alone won't work; They don't get to the tumor, or if they do get to the cancer cells, they get tired trying to kill the cancer cells and fail.


Stephan has designed a material that is safe for humans and can carry cancer-fighting cells into tumors." In addition to minimizing side effects on patients, our ultimate goal is to make t-cell therapy faster, cheaper and easier to deliver to patients," he said.


To do this, Stephan's new study loads car-t cells targeting ovarian cancer onto a porous mesh of metal membranes, which are then placed on the tumor.


"It's not just a passive delivery device. It is also a release platform for triggering the proliferation of car-t cells, which can overcome the tumor's defense against these T cells."


The researchers used thin, almost translucent metal membranes made by Monarch Biosciences. The metal film, which is 10 microns thick and made of Nitinol alloy, can be safely implanted into the body and used in other medical devices.


Under powerful microscopes, the metal film has tiny Spaces that can be configured into different patterns. This space can be filled with drugs or other fluids, and the metal membrane can be implanted into the body, where the fluids leak out and find their targets.


Stephan and his colleagues wanted to see if the metal membrane could contain T cells and deliver those cancer-fighting cells to tumors.


"We needed to find a spatial pattern of metallic membranes that was very suitable for t-cells. The spatial pattern must be small enough not to let the cells fall between the cracks, but not so small that the T cells feel too crowded to move."


They found that a linear pattern, similar to the top-down maze view, best suited to T-cells. They coated the metal membrane with a variety of materials, allowing car-t cells to grow and multiply once inside the body.


The researchers loaded the metal membrane with car-t cells that were programmed to look for the ovarian cancer cell marker ROR1.These genetically engineered car-t cells were placed on either side of the metal membrane and then absorbed into the center of the coated material.


"It's like a loaf of bread with orange sauce on both sides," Stephan said. This metal membrane is the bread, and then we put the car-t cells on the sides of it, and these cells are then immersed in the middle."


Using a laboratory model of ovarian cancer, the researchers implanted a metal membrane containing car-t cells into the tumor. T cells migrate from the metal membrane and metastasize to the vicinity of the tumor. Within 10 days, all the tumors in the mice had disappeared. Within 20 days, 70 percent of the mice remained tumor-free.


If confirmed by more research and clinical trials, the method of implanting metal membranes to inhibit tumor growth could eventually be used to treat diseases such as pancreatic and ovarian cancer.


In another experiment, the researchers found that tubular metal membranes impregnated with car-t cells prevented tumors from growing into such membranes. The method can be used to treat cancers that cause obstruction of the airway or digestive system, such as lung, pancreatic or esophageal cancers, in which stents are used to suppress the tumor's interference with swallowing.


"We are focusing on car-t cells in our current experiments, but I can see this approach working with t-cell receptor therapies, natural killer cells and other immune cells that target cancer," Stephan said.


Reference:1.Michael E. Coon et al. Nitinol thin films functionalized with CAR-T cells for the treatment of solid tumours. Nature Biomedical Engineering, 2019, doi:10.1038/s41551-019-0486-0.


2.Scientists show thin metal mesh loaded with T cells shrinks solid tumors