"Goldilocks" sets of immune cells cause dramatic shrinkage of tumors
Cancer therapies that harness and enhance a patient's unique immune response hold great potential as personalized forms of treatment, and a new tool developed at Northwestern University could expand the availability and effectiveness of this technology. The novel device can be used to sort and multiply harvested immune cells with great efficiency, creating armies of cancer-killing cells that have been deployed to induce dramatic tumor shrinkage in mice.
These types of treatments are known as adoptive cell therapies, and seek to make use of the immune system's natural cancer-fighting abilities. Immune cells have the ability to recognize cancerous cells, and adoptive cell therapy involves harvesting certain types of them, multiplying them in a lab and then returning them to the body to seek out and destroy tumors.
Within this field is a type of treatment called tumor-infiltrating lymphocyte (TIL) therapy, which involves harvesting T cells that have already infiltrated a patient's tumor. The T cells are then activated and multiplied before being re-infused into the patient. But this technique does have shortcomings in its current form, with many of the T cells becoming exhausted and ill-equipped to fight the tumors to great effect by the time they are placed back in the patient.
“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, a co-author on the new study. “The problem is, because of the way the cells are harvested, it only works in a very small number of patients.”
O. Kelley and her colleagues at Northwestern University have developed a novel 3D-printed microfluidic device to help address this issue. The platform is sandwiched in between magnets and combines those forces with fluidic drag forces to sort through cells with great efficiency. A tumor sample can be fed into the device, which then identifies the immune cells within it that are most active. The technology is called microfluidic affinity targeting of infiltrating cells (MATIC), and it enables the swift identification of what the researchers call "Goldilocks populations" of cells.
“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 scientists say the MATIC technology recovers 400 percent more tumor-eating cells than current TIL approaches. Deploying these Goldilocks populations of cells into mouse tumors saw them shrink dramatically, or even disappear entirely in some cases, bringing about large improvements in survival rates among the rodents.
“When we take on the development of a new technology, we typically end up with a hammer, and then need to go find a nail,” Kelley said. “We got introduced to problems in cell therapy, and it was immediately apparent that this was a perfect fit.”
According to the scientists, the tool can be easily 3D-printed for use in hospital settings, and Kelley has started a spin-off company to work toward commercialization and improve the technology. One possibility is that it could be adapted to scan blood samples rather than tumor samples for TILs, which would negate the need for surgery as part of the process.
The research was published in the journal Nature Biomedical Engineering.
Source: Northwestern University