Research Profile - More than skin-deep: The quest for a vaccine to treat melanoma

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Developing a vaccine that could prevent cancer is the Holy Grail that researchers around the world pursue. Although the Grail remains elusive, vaccines to treat certain types of cancer – including melanoma – are within reach.

Increasingly, researchers are focusing on using the body's own immune system as the best tool they have to fight cancer – if they can only trigger an immune response.

CIHR-supported researchers in different parts of the country are using different approaches in their common quest to create a vaccine that would stimulate the body's immune system, essentially mobilizing it to destroy the malignant cells that spread throughout the body in advanced cases of skin cancer.

At the Centre hospitalier de l'Université de Montréal, immunologist Dr. Réjean Lapointe is working with his colleague Dr. Denis Leclerc at Laval University in Quebec City to test two potential vaccines. Each vaccine consists of a combination of a virus obtained from the papaya plant and abnormal proteins produced by tumour cells, known as tumour antigens.

The premise behind the vaccines is that they will stimulate the body's immune system to recognize the abnormal proteins and, by doing so, create an immune response that targets and kills cancerous melanoma cells.

Solid scientific evidence already exists that using immune therapy kills tumours, says Lapointe. But at present, the therapy involves a complicated, difficult and expensive protocol that works in about 50 percent of patients.

"Now we need to simplify that and make it work in the highest proportion of patients," he says.

That's why Lapointe is particularly excited about Leclerc's use of the papaya mosaic virus.

Virus-like particles derived from the papaya mosaic virus do not affect human cells, but can trigger the immune system. Lapointe and Leclerc are inserting tumour antigens into the virus and creating candidate vaccines. If they work, the vaccines would be less expensive to manufacture than current vaccines, most of which are egg-based and take months to produce.

Currently, Lapointe and Leclerc are testing the candidate vaccines against cancerous human cells in a laboratory setting. Although Lapointe and Leclerc are still some years away from clinical trials on humans, "so far, we have had success with two different targets," says Lapointe.

At the University of British Columbia in Vancouver, Dr. Jan Dutz is focusing on testing an adjuvant, or a "helper" that would work with a vaccine to boost the immune system and use its natural processes to defeat metastatic melanoma – skin cancer that has spread beyond the original tumour site. Eventually, Dutz may be involved in developing a candidate vaccine as well.

Currently, his lab is using chemicals applied to the skin to activate the so-called "killer" T-cells that initiate the body's immune response to viruses – or, in the case of melanoma, cancerous cells.

"The concept is that at the time of the injection of a vaccine, putting a cream around the injection site makes the body think there's an infection and improves the response to the vaccine," says Dutz, who is a dermatologist and rheumatologist.

In his lab, Dutz applies a cream that he has developed to boost immune response at the injection site, and then uses chemotherapy on animal models to destroy melanoma tumours. He then studies what proteins and parts of proteins in the tumours the immune system recognizes. His goal is to isolate the tumour proteins that the immune system reacts to as candidates for a vaccine.

Although Dutz and Lapointe and Leclerc's methods may eventually be applicable to other cancers as well, they are focusing initially on melanoma because there is good evidence that the body's immune response is critical in controlling this disease, which is difficult to treat in the advanced stage.

It is also relatively easy for the scientists to evaluate how well the immune system is responding in cases of melanoma, and to observe any regression. That's in part because immune treatments that are effective against melanoma almost invariably induce vitiligo, especially in mice models engineered to have melanoma, says Dutz. vitiligo is an auto-immune disease characterized by changes in skin pigmentation that are easy to observe.

"If it works for melanoma, we plan to apply this (process) to other common cancers – breast, kidney and lung," says Lapointe.

Roughly 920 Canadians die of melanoma every year, and there are about 5300 new cases diagnosed annually, according to the Canadian Cancer Society. If this research leads to a vaccine that can cure melanoma, it would save thousands of lives here and around the globe.

"Melanoma is a skin cancer that's increasing in rate, and we know is one that can be fatal if it's not caught early," says Dutz. "Some people have recurrences of melanoma... many years after their initial cancer has been removed surgically."

Both he and Dutz hope that their approaches to stimulating the immune system will increase the odds for patients.

"The next frontier in our vaccine development is to develop vaccines that will induce long lasting cellular responses," says Dutz.

Cancer immunotherapy is on the edge of making amazing breakthroughs, Lapointe predicts.

"In the next five to 10 years we should see compounds to help mobilize the immune system against cancer that would be authorized agents by the U.S. Food and Drug Administration and Health Canada," says Lapointe.

"If it works for melanoma, we plan to apply this (process) to other common cancers – breast, kidney and lung."
Dr. Réjean Lapointe, Centre hospitalier de l'Université de Montréal