One of cancer’s cleverest tricks is its ability to hide from the immune system. A new approach to cancer treatment called immunotherapy could spare patients at least some of the grueling battery of chemotherapy treatments by retraining the body’s own defenders–the cells of the immune system–to recognize and destroy tumors. Now researchers at Harvard University have developed a simple way to do this inside the body: a polymer implant attracts and trains immune-system cells to go after cancer.
The experimental approach has shown great success in animal studies, increasing the survival rate of mice with a deadly melanoma from 0 to 90 percent. The implant could also be used to treat diseases of the immune system such as arthritis and diabetes, and, potentially, to train other kinds of cells, including stem cells used to repair damage to the body.
Currently when dendrtic cells are trained outside the body most of them died when transplanted.
First, it attracts dendritic cells by releasing a kind of chemical signal called a cytokine. Once the cells are there, they take up temporary residence inside spongelike holes within the polymer, allowing time for the cells to become highly active.
The polymer carries two signals that serve to activate dendritic cells. In addition to displaying cancer-specific antigens to train the dendritic cells, it is also covered with fragments of DNA, the sequence of which is typical of bacteria. When cells grab on to these fragments, they become highly activated. “This makes the cells think they’re in the midst of infection,” Mooney explains. “Frequently, the things you can do to cells are transient–especially in cancer, where tumors prevent the immune system from generating a strong response.” This extra irritant was necessary to generate a strong response, the Harvard researchers found.
When implanted just under the skin of mice carrying a deadly form of melanoma, the polymer increased their survival rate to about 90 percent. By contrast, conventional immunotherapies that require treating the cells outside the body are 60 percent effective, says Mooney.
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.