The recovery and expansion of highly potent tumor-infiltrating lymphocytes (TILs) are key for adoptive cell therapies. Unfortunately, TILs in tumors are rare and challenging to isolate. Now, a team from Northwestern University has developed a new tool to harness immune cells from tumors. This configurable, microfluidic device, which leverages specific expression levels of target cell-surface markers to efficiently recover potent TILs from solid tumors, could help fight cancer rapidly and effectively.

The team’s findings showed a dramatic shrinkage in tumors in mice using this technology compared to traditional cell therapy methods. Using the microfluidic device, the team multiplied, sorted through, and harvested hundreds of millions of cells, recovering 400% more of TILs than current approaches.

This work is published in Nature Biomedical Engineering in the paper, Efficient recovery of potent tumor-infiltrating lymphocytes through quantitative immunomagnetic cell sorting.

Shana O. Kelley, PhD, professor of biochemistry and molecular genetics, Northwestern University Feinberg School of Medicine

“People have been cured in the clinic of advanced melanoma through treatment with their own immune cells that were harvested out of tumor tissue,” said Shana O. Kelley, PhD, professor of biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine. “The problem is, because of the way the cells are harvested, it only works in a very small number of patients.”

Using a new technology called microfluidic affinity targeting of infiltrating cells (MATIC), researchers can pinpoint which cells are most active through cell sorting techniques enabled with nanotechnology. The device, the authors wrote, “which is sandwiched by permanent magnets, balances magnetic forces and fluidic drag forces to sort cells labeled with magnetic nanoparticles conjugated with antibodies for the target markers.”

Mice treated with a novel approach to cell therapy saw dramatic shrinkage in tumors compared to those treated with traditional cell therapy approaches. [Shana Kelley Lab / Northwestern University]
Scientists used MATIC to find what the authors called the “Goldilocks population” of cells, producing dramatic results for the mice population they were looking at. Tumors in mice shrank dramatically—and in some mice disappeared completely—producing a large improvement in survival rates compared to more traditional methods of TIL recovery.

Compared with conventional cell sorting, the authors wrote, immunomagnetic cell sorting “recovered up to 30-fold higher numbers of TILs, and the higher levels and diversity of the recovered TILs accelerated TIL expansion and enhanced their therapeutic potency.” It also allowed the researchers to identify and isolate potent TIL subpopulations. In particular, they wrote, TILs with moderate levels of CD39 (a marker of T-cell reactivity to tumors and T-cell exhaustion).

“Instead of giving mice this mixture of cells with different phenotypes, we’re giving them the one cell phenotype that can actually help them,” Kelley said. “You see much more potency and a much higher response rate when you really home in on the sweet spot of T-cell reactivity.”

The 3D printable device can be easily reproduced and moved between labs and hospitals. A tumor sample enters the device, and high potency tumor-eating cells are spit out. [Shana O. Kelley Lab/Northwestern University]
Because the technology is small and easily reproducible, Kelley said it would be feasible to bring the 3D-printed device into hospital settings, rather than confining it to a lab. Getting cell therapy closer to patients would dramatically reduce research and development costs and ultimately deliver the treatment to more people.

Now, Kelley is using the device to search for the same types of TILs in blood samples, which would eliminate the need for surgery to remove a small piece of tumor prior to this form of treatment.

Kelley has launched a company to commercialize the device and plans to work with industry partners and collaborators at Northwestern to continue expanding use cases for the tool.

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