Immunotherapy is one of the hottest emerging areas of cancer research. After all, using the body’s own cells to fight cancer can be more effective and less invasive than flooding the entire system with toxic chemicals.
Yubin Zhou, Ph.D., assistant professor at the Center for Translational Cancer Research at the Texas A&M Health Science Center Institute of Biosciences & Technology, is studying how to use light to control the immune system and induce it to fight cancer.
“Although neuroscientists have been using light to stimulate neurons for years, this is the first time the technique, called optogenetics, has been used in the immune system,” Zhou said. In neuroscience, the process involves genetically engineering cells to produce proteins from light-sensitive microbes and results in nerve cells that will either send—or stop sending—nerve impulses when they are exposed to a particular color of light. “Neuroscientists have learned a lot about brain circuits using the technique,” Zhou said, “and now researchers in many other fields are giving it a try.”
Zhou and his collaborators have modified the technique for the immune system. It wasn’t easy: unlike nerve cells, immune cells don’t use tiny electrical impulses to communicate. Additionally, immune cells are located deep in the body and are constantly moving around, so getting the light to them can be difficult.
The development took some ingenuity and cooperation. “We collaborated with Dr. Gang Han at the University of Massachusetts Medical School who does bionanotechnology and photomedicine development,” Zhou said. “Together, we were able to combine state-of-the-art optogenetic approaches with cutting edge nanotechnology.” Called optogenetic immunomodulation, their method was featured in a recently published article in eLife.
“This work was driven by talented scientists in the lab: graduate students Lian He and Peng Tan and postdoctoral research fellow Guolin Ma, Ph.D.,” Zhou said, “who fearlessly undertook this daunting project and overcame all the challenging obstacles to make this technique into reality.”
With this method, the researchers can control the action of immune cells and “instruct” them to kill cancerous tumor cells. They use a near-infrared laser beam, which can penetrate deep—in this context, deep means a centimeter or two—into the tissue, where a nanoparticle turns the near-infrared light into blue light, and that directs the activity of genetically engineered immune cells. “We are able to wirelessly control the action of immune cells buried deep in tissue,” Zhou said.
The team genetically engineered immune cells so that a calcium gate-controlling protein became light sensitive. When they are exposed to the blue light emitted by the nanoparticle, their calcium ion gates open. When the light is turned off, the gates close. More light leads to a greater flow of calcium, so the researchers are able to finely tune the calcium-dependent actions of immune cells to fight against invading pathogens or tumor cells.
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