T-VEC, for example, has been altered to drastically reduce its ability to cause herpes. As more researchers entered the field and initiated small clinical tests, they began to produce enticing anecdotes. A tumour on the left side of her forehead had degraded the bone underneath and was putting pressure on her brain. Yet treatment with an experimental virus sent her into complete remission S.
Russell et al. Mayo Clin. But statistics — not anecdotes — rule over drug approvals. In , regulators in China approved an oncolytic adenovirus called H to treat head-and-neck cancer, after evidence showed that the treatment could shrink tumours. Those trials stopped short of assessing improvements in patient survival — a measure often required for FDA approval.
Since then, a medical-tourism industry has built up in China for people who cannot get the therapy in their home countries. Andtbacka et al. The virus both shrank tumours in people with advanced melanoma and extended patient survival by a median of 4. Is this an active agent or not? He and others note that the therapy — which must be injected directly into tumours — seemed to rein in cancer elsewhere in the body as well. This is a sign that results are real and that the virus sparked an immune response as intended, Thompson says.
In June , a small clinical trial by Amgen suggested that this combination may boost effectiveness over that of the immunotherapies alone. And researchers continue to look for ways to improve T-VEC.
In particular, they would like to be able to deliver the therapy systemically, so that the virus could target tumours in organs that are difficult to reach with an injection. This would require a technique to prevent the body from mounting an immune response to the virus prematurely, which would disable it before it could reach and kill tumour cells, says Howard Kaufman, a cancer researcher at Rutgers Cancer Institute of New Jersey.
Today, several dozen viruses—and a few strains of bacteria—are being studied as potential cancer treatments, according to research presented at an NCI-sponsored conference on using microbes as cancer therapies in Although the notion of using viruses in cancer therapy is old, the science only began to move forward in the s with advances in genetic engineering technology, noted Matthias Gromeier, M. Gromeier continued. The treatment, which is injected into tumors, was engineered to produce a protein that stimulates the production of immune cells in the body and to reduce the risk of causing herpes.
In some patients receiving the therapy, tumors that could not be injected have shrunk, suggesting that T-VEC can generate a systemic immune response, noted Howard Kaufman, M. Kaufman, who co-led the clinical trial that led to the approval of T-VEC. At the NCI meeting about using microbes as cancer therapies last year, more than investigators discussed many topics, including the need to better understand how infectious agents interact with tumors and with components of the immune system.
Some viruses work primarily by killing tumor cells, whereas others work by directing local or systemic immune responses, he explained. Kaufman noted that T-VEC, when given alone or in combination with other therapies, generally has been well tolerated by patients in clinical trials.
One of the challenges for researchers now is to try to enhance the immune response to the tumor through a variety of strategies, including by combining oncolytic virus therapy and immunotherapy. The promise of this approach has been demonstrated in two early-phase clinical trials. Patients with melanoma who received T-VEC plus a type of immunotherapy known as a checkpoint inhibitor had higher response rates than those who received a checkpoint inhibitor alone.
The results suggested to the researchers that the combination therapy could induce an immune response. Chesney, who co-led the clinical trial with Dr. The oncolytic virus induced the infiltration of immune cells known as T cells into tumors that had low levels of these cells prior to treatment, the researchers found. Haanen, Ph. The therapy was generally well tolerated, he noted, and the most common side effects were fatigue, fever, and chills.
A phase 3 clinical trial involving patients with melanoma who will receive T-VEC with or without pembrolizumab is under way to assess the combination therapy in a large, randomized study. This NCI-sponsored trial is testing the idea that injections of T-VEC into accessible melanoma tumors will increase the infiltration of immune cells into these and potentially other tumors, making them susceptible to treatment with pembrolizumab.
Most oncolytic virus therapies have been tested in patients with melanoma or brain tumors, and most treatments have been given as injections into tumors. Two new studies highlight efforts to expand the number of cancer types treated with oncolytic virus therapies as well as the methods of delivery. One of the studies found that an oncolytic virus delivered intravenously could cross the blood—brain barrier and enter brain tumors , killing tumor cells.
The treatment uses a type of virus known as a reovirus, which causes mild symptoms of a cold or stomach bug in children. In the second study, researchers tested the Maraba virus, which was originally isolated from a species of sand fly in Brazil, as a way to sensitize tumors to immunotherapy in a mouse model of triple-negative breast cancer.
An immunotherapy approach using the Maraba virus above and checkpoint inhibitors cured aggressive breast cancer in mice. At the Duke Cancer Institute, Dr. When the research began in the mids, Dr. Gromeier viewed oncolytic viruses primarily as agents for killing cancer cells. His thinking changed, however, as PVS-RIPO was tested in patients , and his team noticed clinical changes associated with immune responses in the patients.
Gromeier recalled. To learn more about the mechanisms by which poliovirus therapy attacks tumor cells, the Duke researchers recently conducted experiments in cancer cell lines and in mice.
They found that cancer cells infected with PVS-RIPO released tumor antigens and other material that activated immune cells called dendritic cells and induced an immune response against the cancer cells. The finding provides further support for testing the oncolytic virus in combination with other types of immunotherapies, including checkpoint inhibitors, she added. Two weeks before undergoing surgery, the patients will receive injections of the treatment into their tumors and will be followed to determine whether the poliovirus triggers any changes in immune system molecules or in the tumor.
As oncolytic viruses are tested in clinical trials, researchers will try to learn which patients are likely to respond. Another challenge for the field will be to use the knowledge gained from the melanoma clinical trials to develop treatments for patients with other types of tumors, Dr.
Chesney noted. Fueyo of MD Anderson. The evolution in thinking about oncolytic viruses since Dr. Fueyo began working in the field two decades ago represents an important shift that has implications for future research. November 18, , by NCI Staff.
October 22, , by NCI Staff. October 15, , by NCI Staff. The future of viruses Dr. Related Articles How can a virus cause cancer? Should cancer patients get the flu shot? Cancer vaccines do exist, but don't expect the impossible. Donate to Gateway for Cancer Research Make a difference in the fight against cancer by donating to cancer research.
Publication types Research Support, N. Gov't Review.
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