Viruses may be key as cause, cure for cancer

Today’s weapons in the war against cancer are surgery, radiation and chemotherapy; researchers, however, hope that a fourth will soon be added to the arsenal.

It is one that could scarcely have been imagined a few decades ago and, as John Bonner writes in the May 7 issue of Chemistry & Industry, one that soon may revolutionize cancer therapy. The most rapidly growing field of immunology, says Bonner, is the search for a “cancer vaccine.”

Viruses are key to a cancer vaccine. That may seem strange at first, as we normally think of viruses as the cause, not the cure, for diseases ranging from the common cold to AIDS. Viruses also may be a factor in causing certain cancers.

The National Cancer Institute and U.S. Department of Health, Education and Welfare issued a report called the “The Virus Cancer Program” in August 1976. The report says that the Epstein-Barr virus, a type of herpes virus, has been implicated as a causative agent for a cancer called Burkitt’s lymphoma, while a similar link has been found between herpes simplex virus type 2, or HSV-2, and squamous cell carcinoma of the uterine cervix. In 1976, research emphasized the role of intact viruses in all types of human cancer, and the idea that genes, or their products, might be causative agents was just starting to surface.

Bonner says that the idea of a viral-based cancer vaccine came about almost by accident. In the 1890s, Dr. William Coley witnessed the spontaneous remission of bone cancer in a patient who also had a severe skin infection called erysipelas. Mystified, Coley assumed the cancer remission was somehow linked to the skin disease and tested his theory by injecting cancer patients with the bacteria responsible for erysipelas. He tested more than 900 patients with varying degrees of success until his death in 1936.

Other doctors largely ignored Coley’s work and it was not until the late 1950s, writes Bonner, that the field of immunology gave an explanation for his results. Researchers had learned that while the body’s immune system was efficient at recognizing and destroying foreign cells such as bacteria and virus, it was much less so in combating cancer cells. The reason is that the antigens, molecules found on the surface of cells that can trigger an antibody response, of healthy and cancerous cells are often enough alike so that the body’s immune system cannot distinguish between them. Somehow products from the bacteria that caused erysipelas in Coley’s patient had preferentially concentrated in his cancer causing the immune system to attack it.

The trick to developing a cancer vaccine, writes Elizabeth Pennisi in the Nov. 13, 1998, issue of Science, is to use viruses that are either naturally harmless to humans, or genetically altered to render them so, and will also preferentially congregate in the tumor. These viruses will trigger an immune response at the site that it is hoped will kill the cancer cells along with the foreign invader.

One of the most promising of the new virus-based vaccines is described by Patrick Lee et al. in the same issue of Science. Lee’s group uses a reovirus, a virus common in the lungs and gut and harmless to healthy tissue but deadly to cancerous cells. The reason is that the virus multiplies rapidly when it encounters a metabolic pathway found in cancerous cells. Lee’s group infected lab mice with glioblastoma cells, a type of invariably fatal brain cancer, followed by injections of reovirus. They found that the tumors shrank or disappeared in 80 percent of the mice tested. Similar encouraging responses were obtained with 25 other human cancer cell lines.

In another example of taking advantage of the cancer cell’s own metabolic processes, Frank McCormick and his colleagues at ONYX Pharmaceuticals in California describes in the Oct. 18, 1996, issue of Science how they have produced a genetically altered adenovirus that cannot reproduce in healthy cells but proliferates in a cancer cell that lacks the p53 tumor suppressor gene. As a result, the virus sets up a massive, and fatal, immune response in the tumor cells while producing no more than flulike symptoms in the patient. Since loss of the p53 gene contributes to half of all human cancers, McCormick’s group hopes that its work will lead to a vaccine against lung, colon and breast cancers among others.

Finally, George Martuza of Georgetown University heads a group that genetically altered a herpes virus that causes encephalitis so that it grows in cancerous cells while leaving healthy ones alone. In the May 10, 1991, issue of Science, they describe how glioblastoma cells in mice were virtually destroyed while surrounding healthy tissue remained unscathed. Although this was a paper appearing early in the cancer vaccine literature, Martuza made the prescient prediction that “genetically altered viruses are worthy of further exploration as a means of therapy for malignant tumors resistant to currently available treatments.”

As Pennisi points out, both viruses and cancer have spawned their share of human misery over the years. It seems somehow fitting that medical science is now recruiting the aid of one to combat the other.

Clair Wood taught chemistry and physics for more than 10 years at Eastern Maine Technical College.