Using virus to fight cancer

When a virus infects a tumor cell, the virus makes copies of itself until the cell bursts. This can lead to an immune response against nearby tumor cells a local response or tumor cells in other parts of the body a systemic response. For this reason, some researchers consider oncolytic viruses to be a form of immunotherapy —a treatment that harnesses the immune system against cancer.

But many in the field would agree that more studies are needed to learn how different oncolytic viruses work against cancer.

Since the late s, doctors have observed that some patients with cancer go into remission, if only temporarily, after a viral infection. 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. Although the initial findings are promising, using viruses to fight cancer is still very much in its infancy. Tan, who has used the therapy to treat patients, is optimistic about its future.

But research is underway to test how other oncolytic viruses may be used to treat patients with brain tumors and sarcomas, as well as breast, lung, liver and bladder cancers. I think modern-day medicine is on the right track, though, and combining therapies is a major piece of that.

Make a difference in the fight against cancer by donating to cancer research. The virus can also be used to deliver what are known as suicide genes.

In this case, the measles virus will then be able to recognize a special receptor that is often prevalent in cancer cells. Here the virus is allowed into the cancer cell, where it proliferates and essentially forces the cell to commit suicide. A further application is the introduction of genes that stimulate the immune system against the spread of cancer cells.

The immune response is much stimulated in patients who received a measles vaccination in their childhood and are now confronted with the virus again as part of their cancer treatment. With the disintegration of cancer cells, not only viral components are released, but also very many tumor components.

This mixture has a highly stimulating effect on the immune system. However, this is not only recognized by the viral proteins, but also the proteins of the cancer cells, said Lauer. If a vaccination has taken place, however, it's possible that the viral component can be caught before ever reaching the cancer cell.

Patients who receive oncolytic treatments have generally already undergone radiation therapy and several courses of chemotherapy. The studies currently being conducted are also testing for the potential problems of oncolytic therapy. Stem cells, e. This immunity, however, is defective in cancer cells, which allow the virus to gain entrance to the cells with ease. At this point scientists still believe that the oncolytic measles virus is no more harmful than any measles vaccination, a treatment that has been practised for decades.

In a way, viruses can be thought of as activators of the immune system. Normally, your immune system ramps up its response to combat the virus, often clearing the infection. The immune system plays an important role in fighting off other infections and diseases as well, including cancer.

Simulating OV treatment in the lab OVs are promising biological therapies to treat cancer. Building a stronger OV to fight brain cancer Glioblastoma multiforme is one of the most aggressive and common brain cancers that primarily affects adults. They hope to improve the immune-stimulating effects of this OV to better treat people with glioblastoma multiforme.