Magnets can help kick start cancer-killing T cells and increase their power, according to a new study of mice with the deadly skin cancer melanoma.
For the research, scientists used a magnetic field to cluster closer together nano-sized artificial white blood cells and the T cell receptors to which they bond.
That clustering process activated dormant, or “naive,” T cells and ramped up the immune response of T cells already turned on, researchers say in a report published online in the journal ACS Nano.
The T cells stopped the growth of melanoma tumors; by the end of the experiment, tumors in mice treated with artificial white cells and magnetism were about a tenth the size of those in untreated mice. Six of the eight magnetism-treated mice survived for more than four weeks showing no signs of tumor growth. None of the untreated mice survived.
“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 Karlo Perica, a graduate student at the Institute for Cell Engineering at Johns Hopkins University School of Medicine. “We think this is the first time magnetic fields have acted like medicine in this way.”
The magnets are only part of the explanation for the experiment’s success, says Jonathan Schneck, the lead researcher and professor of pathology, medicine, and oncology. The tiny artificial white cells are the other.
Smaller the better
“Size was key to this experiment,” he says. “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.”
Schneck’s team has pioneered the development of the artificial white blood cells, known as artificial antigen-presenting cells, or aAPCs. The particles show promise in training animals’ immune systems to fight cancer and other diseases.
To do that, the aAPCs must interact with the naive T cells in the body awaiting instructions about which specific invading disease they will battle.
The aAPCs bind to specialized receptors on the T cells’ surfaces and “present” them 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 Schneck team has been working with microscale particles, about one-hundredth of a millimeter across. But, aAPCs of that size are still too large to get into some areas of a body and may even cause tissue damage. The team began to explore using much smaller nanoscale aAPCs, which can be measured in billionths of a meter. Perica tested their impact.
Best magnetic dose?
The nano-aAPCs were small enough that many of them could bind to a single T cell, as the team had expected. But when Perica compared naive T cells to those that had been activated, he found that the naive cells were able to bind more nanoparticles.
“This was quite surprising, since many studies had already shown that naive and activated T cells had equal numbers of receptors,” Schneck says. “Based on Karlo’s results, we suspected that the activated cells’ receptors were configured in a way that limited the number of nanoparticles that could bind to them.”
To see whether moving the receptors would help, Perica used small (quarter-sized) but strong magnets to apply a magnetic field to the cells, causing the nano-aAPCs to attract one another and cluster together, bringing the receptors with them. The team then tested the magnetically treated T cells in living mice with skin tumors.
“We have a bevy of new questions to work on now,” Schneck says. “What’s the optimal magnetic ‘dose’? Could we use magnetic fields to activate T cells without taking them out of the body? And could magnets be used to target an immune response to a particular part of the body, such as a tumor’s location? We’re excited to see where this new avenue of research takes us.”
The National Institute of Allergy and Infectious Diseases, the National Cancer Institute, Miltenyi Biotec, and the Cancer Research Institute supported the work.
Under a licensing agreement between NexImmune and the Johns Hopkins University, Schneck is entitled to a share of royalties received by the university. Schneck also owns NexImmune stock, subject to restrictions under university policy. He is a member of the company’s board of directors and scientific advisory board, an arrangement managed by the Johns Hopkins University in accordance with its conflict of interest policies.
Source: Johns Hopkins University