Novel Cancer Therapy ‘Farms’ Natural Killer Cells

A new promising therapy has emerged that deploys the body’s ‘natural killer’ immune cells to fight cancer. The researchers have developed the first systematic approach to catch natural killer cells and release cancer-killing packets called exosomes. These exosomes are thousand times smaller than the natural killer cells and are able to penetrate the cancer cell’s defenses. The research conducted at University of Michigan Rogel Cancer Center and U-M College of Engineering is published in the journal Advanced Science.

A study conducted in which blood samples were collected from five patients with non-small cell lung cancer showed that the approach was able to capture natural killer cells on a microfluidic chip and use them to ‘farm’ the NK exosomes. The researchers were also able to demonstrate that the exosomes could effectively kill circulating tumor cells in cell cultures.

Co-lead author of the study, Yoon-Tae Kang, Ph.D., a research fellow in chemical engineering said, “Exosomes are small sacs of proteins and other molecules that are naturally released by almost every type of cell in the body. In this case, we wanted to expand our understanding of NK exosomes and try to harness their cancer-killing potential.”

NK exosomes are stable and easy to modify for therapeutic purposes and they can also help in diagnosis and monitoring cancer.

One of the disadvantages of NK cells is that after injection, they are not able to infiltrate the tumor microenvironment. However, NK cell-derived exosomes contain the same cancer-killing molecules but they’re much, much smaller and are able to penetrate into the tumors.

Harvesting Exosomes

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Trying to isolate exosomes directly from the blood is a difficult process.

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The NK exosome harvesting system has three steps. In the first step, the natural killer (NK) cells are captured on a graphene oxide microfluidic chip developed at U-M. In the second step, the cells are incubated prompting them to release exosomes which are captured by tiny magnetic beads, called ExoBeads, which are coated with exosome-specific antibodies. The beads are then removed from the chip and the exosomes are seperated by a different process.

By using a liquid biopsy system called Labyrinth developed at U-M, the circulating tumor cells from patient blood samples were isolated to evaluate the correlations between NK cells and exosomes, and circulating tumor cells.

The researchers found that more NK cells were present in the sample indicating fewer circulating tumor cells. They also found that more tumor cells were in a sample indicate more NK exosomes were present. This shows that the presence of cancer stimulates the NK cells to produce the cancer-fighting exosomes.

Additional experiments showed that circulating tumor cells in cell cultures were killed by the NK exosomes derived from patient samples.

The researchers noted that the exosomes have good potential and can be further engineered and optimized to be more potent and efficient against cancer cells.

Senior co-author Nithya Ramnath, MBBS, an oncologist and professor of internal medicine at Michigan Medicine said, “ Immunotherapy approaches that target immune checkpoints have revolutionized cancer therapy for several cancers. However, only a small minority of patients exhibit a durable clinical benefit and cure. Preliminary studies with NK cells either by themselves or in combination with immune checkpoint inhibitors have, however, have shown only modest results. NK-derived exosomes, on the other hand, are able to home into tumors more effectively. The current paper represents a technological advance in the ability to harvest not only NK cells, but also NK derived exosomes that could help inform future immunotherapeutic approaches.”

Source-Medindia