Melanoma is all too often a deadly disease. While it accounts for less than 5% of all skin cancers, it is responsible for more than 75% of skin cancer deaths. This is because it is very difficult to treat once it has spread beyond where it started.

But the knowledge gained over the past few decades may soon lead to new, more effective forms of treatment for the disease. Most of these new treatments, such as cancer vaccines now in development, try to use the body’s immune system to attack the cancer cells.

Immunotherapy has thus far had a limited role in treating cancer, but it is one of the most promising areas of cancer research, especially in melanoma. This cancer seems to be especially well suited for research with immunotherapy treatments for several reasons:

With these factors in mind, researchers have been trying to make vaccines against melanoma for many years, often with mixed results.

Most people are familiar with the vaccines given during childhood to prevent certain diseases, such as measles and mumps. These vaccines work by teaching the body’s immune system to recognize a specific invader, such as a virus, so the body can resist infection if exposed to it in the future.

Cancer vaccines operate on the same principle, attempting to prime the immune system to combat a disease. But there are some important differences. Most cancer vaccines now in development are not meant to prevent disease, but to stop it from returning after most or all of it has been removed during surgery.

Viruses and bacteria look very different from cells in the body, so the immune system has a relatively easy time recognizing them as “foreign.” It knows they don’t belong in the body, so it doesn’t take much prodding to stimulate an attack on these organisms. Cancer cells, on the other hand, look a lot like normal cells, so the immune system has a harder time distinguishing between the two.

The trick is to find something different about the cancer cells and make the immune system aware of this. But this has not proved to be an easy task. Scientists have used a variety of techniques to try to get the immune system to attack melanoma cells, and each has its advantages and disadvantages.

The simplest technique has been to use whole, killed melanoma cells as a vaccine. There are two possible sources of such cells.

The vaccine can be made from a person’s own melanoma cells (removed during surgery), which is known as an autologous vaccine. These have the advantage of having all of the needed “flags” (antigens) on the cell surfaces to cause the immune system to respond.

But because the immune system has already seen these cells and has not killed them off, they have to be chemically modified and usually must be given along with an immune booster to make them more effective. Other disadvantages with such personalized vaccines include the expense to make them, and the fact that some people do not have enough cells removed during surgery to make an adequate amount of vaccine.

Still, early results have shown that some people seem to live longer when given the vaccine. At least one such vaccine, known as M-VAX, is now in late-stage clinical trials, the results of which should be available within the next few years.

The other sources of tumor cell vaccines are melanoma cells taken either from other patients or grown in a lab. These are known as allogeneic vaccines.

Two such vaccines are now in large clinical trials – Canvaxin (which combines three types of irradiated melanoma cells) and Melacine (which uses two types of melanoma cells that have been split apart to expose more antigens). A recent review of previous studies of Canvaxin showed it may increase survival time. The largest study of Melacine to date did not find an overall survival advantage, but did find a benefit in people with specific immune system characteristics, which may be explored in further studies.

In the last decade, scientists have come to understand more about what makes melanoma cells different from other cells, as well as about how the immune system works. These discoveries have led to newer, more specific types of vaccines, which are now entering clinical trials.

Many of the “flags” on cell surfaces (known as antigens) that are unique to melanoma cells have been identified, and researchers are now making vaccines composed of one or more of these antigens. These might have the advantage of more specifically activating the immune system. (Whole cell vaccines, on the other hand, may not have enough of these antigens, and have many unneeded antigens.)

Other vaccines use pieces of antigen DNA, which are taken up by cells in the body and provide a more constant source of antigen exposure to the immune system.

Still others involve taking immune system cells out of the body, where they can be exposed to the antigens in the lab and then reintroduced into the body. Most of these vaccines use dendritic cells, which are a very powerful type of immune system cell.

Researchers recently had success with a similar technique that involved taking immune system cells known as tumor infiltrating lymphocytes (TILs) from surgically removed tumors, growing them in the lab, and reinjecting them. While only a small number of patients were treated with this approach, almost all had their tumors shrink.

Unfortunately, no vaccine has yet received FDA approval for treating melanoma, so these therapies are currently available only through clinical trials. But with the wealth of new techniques being explored to help treat melanoma, the outlook for advanced cases will undoubtedly improve.