One of the most important findings in cancer research in the past two decades is that tumors can create force field-like protection against the immune system. A new study has identified a way to break through that force field to improve cancer treatment, by taking advantage of a virus that can specifically infect cancer cells.
Oncolytic viruses, as these cancer cell-infecting viruses are known, thrive inside cancer cells. There, they replicate rapidly, destroying the cells by breaking them open and also exposing the cell’s contents to the immune system. Not only do these viruses naturally disrupt cancer, but they can be modified to carry other genes directly into cancer cells that boost the treatment’s ability to destroy tumors.
One oncolytic virus, an immunotherapy called T-VEC, has been approved by the Food and Drug Administration (FDA) for the treatment of metastatic melanoma. Oncolytic virus therapies for additional types of cancer have yet to be approved, although several are being tested in clinical trials.
In the new study, funded in part by NCI, Greg Delgoffe, Ph.D., of the University of Pittsburgh School of Medicine, and his colleagues created a modified oncolytic virus that can transport the genetic instructions for a potent cancer treatment directly into cancer cells.
Those instructions cause the cell to produce a protein that blocks the activity of another protein, called TGF-beta, that helps protect cancer cells from being attacked by the immune system.
In mice with head and neck tumors, treatment with the modified virus shrank tumors that could not be affected by the nonmodified oncolytic virus, according to findings published in the October 2 issue of the Journal of Experimental Medicine. The researchers also found that combining the modified oncolytic virus treatment with another type of immunotherapy was even more effective than the oncolytic virus therapy alone.
In addition to demonstrating the potential of using a virus to deliver a drug “payload,” said James Gulley, M.D., Ph.D., co-director of NCI’s Center for Immuno-Oncology, the new study is “another piece of the puzzle showing the importance of TGF-beta” in suppressing the immune response against cancer.
Many experimental drugs block TGF-beta, Dr. Gulley continued, but they often cause serious side effects because they also affect healthy cells. The oncolytic virus developed in this study “is interesting,” he said, because it blocks TGF-beta in tumor cells only, which could reduce side effects from the treatment.
