Applying a magnetic field caused the nano-aAPCs (iron nanoparticles with T-cell-activating proteins) --- and their receptors on T-cells --- to cluster
Johns Hopkins researchers have trained the immune systems of mice to fight melanoma, a deadly skin cancer, by using nanoparticles designed to target cancer-fighting immune cells, The experiments, described in ACS Nano February 24, represent a significant step toward using nanoparticles and magnetism to treat a variety of conditions, the researchers say.
“By using small enough particles, we could, for the first time, see a key difference in cancer-fighting cells, and we harnessed that knowledge to enhance the immune attack on cancer,” said Jonathan Schneck, M.D., Ph.D., a professor of pathology, medicine and oncology at the Johns Hopkins University School of Medicine‘s Institute for Cell Engineering.
Schneck’s team has pioneered the development of artificial white blood cells (“artificial antigen-presenting cells” or aAPCs), which show promise in training animals’ immune systems to fight diseases such as cancer. To do that, the aAPCs must interact with immune cells known as naive T cells that are already present in the body, awaiting instructions about which specific invader they will battle.
The aAPCs bind to specialized receptors on the T cells’ surfaces, “presenting” the T cells with distinctive proteins called antigens. This process activates the T cells, programming them to battle a specific threat such as a virus, bacteria, or tumor, as well as to make more T cells. The team had been working with microscale particles, which are about one-hundredth of a millimeter across. But, says Schneck, aAPCs of that size are still too large to get into some areas of a body and may even cause tissue damage because of their relatively large size. In addition, the microscale particles bound equally well to naive T cells and others, so the team began to explore using much smaller nanoscale aAPCs.
Since size and shape are central to how aAPCs interact with T cells, Karlo Perica, a graduate student in Schneck’s laboratory, tested the impact of these smaller particles. To see whether there indeed was a relationship between activation and receptor clustering, Perica applied a magnetic field to the cells, causing the iron-based nano-aAPCs to attract one another and cluster together, bringing the receptors with them. The clustering did indeed activate the naive T cells, and it made the activated cells even more active — effectively ramping up the normal immune response.
To examine how the increased activation would play out in living animals, Perica tested the impact of these smaller particles.treated a sample of T cells with nano-aAPCs targeting those T cells that were programmed to battle melanoma. The researchers next put the treated cells under a magnetic field and then put them into mice with skin tumors.
The tumors in mice treated with both nano-aAPCs and magnetism stopped growing, and by the end of the experiment, they were about 10 times smaller than those of untreated mice, the researchers found. In addition, they report, six of the eight magnetism-treated mice survived for more than four weeks showing no signs of tumor growth, compared to zero of the untreated mice.
“We were able to fine-tune the strength of the immune response by varying the strength of the magnetic field and how long it was applied, much as different doses of a drug yield different effects,” says Perica. “We think this is the first time magnetic fields have acted like medicine in this way.”