Robert Langer, a pioneer in developing drug-delivering polymers and an Institute Professor at MIT, says that Mooney’s work is “a really beautiful combination of materials science and cell technology.”
Accomplishing the entire immunotherapeutic process inside the body using a common polymer is “incredible,” adds Peter Polverini, dean of dentistry and a professor of pathology at the University of Michigan, and a specialist in oral cancer. “From the standpoint of efficacy and efficiency, this is a huge advance.” For patients, he says, a subcutaneous implant would be “far less burdensome” than doctors removing and reimplanting cells.
Mooney developed the polymer systems with more than melanoma in mind, however. He hopes to develop similar implants for treating other types of cancer, which should simply be a matter of changing the antigen carried by the polymer. But the approach could also be used to treat other kinds of immune disorders. For example, different chemical signals could dampen immune cells’ activity in order to prevent transplant rejections and treat autoimmune diseases such as type 1 diabetes and rheumatoid arthritis, which result when the immune system attacks normal tissues. Mooney also hopes that the polymer system can train a different class of cells altogether. Just as fragile dendritic cells seem to respond better to being trained inside the body, this might be a more effective way to recruit and reprogram stem cells.
If proved in people, the cell-training polymers might also bypass some of the regulatory hurdles and expense faced by cell therapies, since devices are more readily approved by the Food and Drug Administration. Indeed, Mooney predicts that the therapy will move quickly through safety tests in large animals (the next step before human trials), and he expects to bring the cancer immunotherapy to clinical trials soon. “All the components are widely used and tested, and shown to be safe,” he says.
One thing that remains to be proved, however, is whether the treatment is effective over the long term–whether the body will recognize the cancer cells months and even years later, after the polymer has biodegraded. Most cancer deaths are caused by secondary tumors called metastases that can arise from just a single cell that leaves the primary tumor. The immune system’s ability to remember disease-causing agents over the long term is one of the reasons that immunotherapy for cancer seems so promising. Once the cells have been trained to recognize and attack a tumor, the immune system should be prepared to combat cancer recurrence. Mooney says that he’s currently working on long-term studies. “Just think what the benefit would be to patients to have their immune system reprogrammed at will to fight disease in a sustained fashion,” says Polverini.