Thin metal films loaded with immune cells show promise as cancer therapy

Researchers at Seattle’s Fred Hutchinson Cancer Research Center have demonstrated the effectiveness of a brand new methodology for getting immune cells to battle stable tumors — by spreading them like jam onto ultra-thin sheets of metal mesh, after which laying the mesh onto the tumors.

To date, the method for delivering genetically engineered T cells has been used solely on mice — however the preclinical examine published today in Nature Biomedical Engineering may assist set the stage for the mesh for use on people as effectively.

“Cell therapies to battle cancer have had nice success in blood cancers, however haven’t labored effectively with stable tumors,” senior examine writer Matthias Stephan, a college member within the Fred Hutch Medical Analysis Division, explained in a news release.

“Our findings take a big step towards making cell therapies efficient in opposition to stable tumors by displaying {that a} skinny metal mesh loaded with T cells engineered to battle ovarian cancer cleared tumors in 70% of the handled mice,” he mentioned.

The mesh is fabricated from a micropatterned nickel-titanium alloy, generally recognized as nitinol. It’s solely 10 micrometers thick, which is thinner than the width of a human hair. Nitinol films are already utilized in a variety of medical gadgets, together with stents which might be implanted in blood vessels to deal with vascular illness.

Stephan and his colleagues have been working for years on a variety of delivery systems for chimeric antigen receptor T cells, higher recognized as CAR T cells. Such cells are programmed to beat the defenses of a affected person’s cancer cells. Though injecting CAR T cells into the bloodstream is efficient in opposition to leukemia and different kinds of blood cancer, that technique seems to be too scattershot to work in opposition to stable tumors.

If CAR T supply programs had been simpler in opposition to stable tumors, they’d be enticing options to chemotherapy and radiation. “Along with minimizing unwanted side effects in sufferers, our final purpose is to make T-cell therapies quicker and cheaper to make, and simpler to ship to sufferers,” Stephan mentioned.

Different researchers have regarded into utilizing scaffolds made of hydrogels or electrospun polymers as T-cell supply platforms, however these supplies might not have the optimum construction to carry excessive concentrations of T cells. Stephan and his colleagues turned as a substitute to skinny films of nitinol.

“We wanted to discover a sample of the movie that may work effectively for T cells,” Stephan defined. “The sample wanted to be sufficiently small the place the cells wouldn’t fall between the cracks, and never too small in order that the T cells would really feel too cramped and wouldn’t be capable to transfer.”

A mesh that was patterned with maze-like straight traces appeared to work greatest. They coated the mesh with supplies that may enable cells to develop and broaden as soon as they’re contained in the physique. Then they loaded the mesh with CAR T cells that had been engineered to seek out and destroy ovarian cancer cells.

“It’s like a bit of bread unfold with marmalade on either side,” Stephan mentioned. “The metal movie is the bread, after which we put CAR T cells on either side of it, after which they soak into the center, too.”

The method was examined on mice that had been injected with human ovarian cancer cells, and developed tumors below their pores and skin as a end result. Ten mice had the T-cell mesh implanted onto their tumors. Ten different mice got CAR T cells by injection, and 10 untreated mice served as a management group.

Inside 10 days, the tumors disappeared within the mesh-treated mice, and 7 of the ten mice remained tumor-free weeks later. In distinction, all the mice receiving the T-cell injections died inside 60 days, and the untreated mice died inside a month.

In one other experiment, the Fred Hutch group discovered {that a} tube-shaped model of the T-cell mesh stored tumors from rising into the tube. They mentioned this strategy could possibly be used in opposition to cancers that trigger obstruction of the respiratory or digestive system, as may be the case for lung cancer or pancreatic cancer. It may be used in opposition to esophageal cancer, the place stents are used to maintain tumors from interfering with swallowing.

Stephan urged that the construction of the metal mesh may come in useful for all kinds of different medical functions. “We targeted on CAR T cells within the present experiment, however I may see this strategy working with T-cell receptor therapies, pure killer cells and different kinds of immune cells that concentrate on cancer,” he mentioned.

Of their analysis paper, the authors acknowledged that their experiments had been achieved below unnatural circumstances. Earlier than the group strikes on to human medical trials, the T-cell mesh method should be evaluated below extra sensible circumstances, with bigger animals. Within the meantime, the researchers are creating completely different mesh patterns, together with hexagonal and spiral designs, in hopes of optimizing the therapeutic impact.

The principal authors of the paper in Nature Biomedical Engineering, “Nitinol Thin Films Functionalized With CAR-T Cells for the Treatment of Solid Tumours,” are Michael Coon and Sirkka Stephan of the Fred Hutch Medical Analysis Division. Different authors embrace Vikas Gupta and Colin Kealey of Monarch Biosciences.

Monarch Biosciences manufactured the mesh used within the examine, and supplied funding for the analysis. Extra funding got here from Fred Hutch and the Bezos Family Foundation. Fred Hutch and a few of its scientists might profit financially from this work sooner or later. Matthias Stephan and Colin Kealey have filed a patent application related to T-cell mesh technology, with Fred Hutch and Monarch Biosciences listed as assignees.
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