Melanoma is the most serious form of skin cancer and accounts for 75 percent of all skin cancer deaths. The American Cancer Society estimates 62,480 new cases of melanoma will be diagnosed this year, and as many as 8,420 people will die from melanoma in 2008.

A researcher at the University of Iowa College of Pharmacy has been granted a four-year $717,000 American Cancer Society Research Scholar Award to develop a vaccine to treat and prevent melanoma. Aliasger Salem, PhD, a member of Holden Comprehensive Cancer Center at the UI, and who will lead the research, talks about melanoma:

Who is at risk to develop skin cancer?

Skin cancer is the most common form of cancer in the United States. More than one million skin cancers are diagnosed annually, and one in five Americans will develop skin cancer during the course of their lifetime.

The exact causes of melanoma are still, to some extent, unknown, and it’s not always clear why one person gets melanoma and another does not. But, research has shown that there are risk factors that result in melanoma being more likely to occur, and these risk factors include:

• A large number of abnormal moles
• More than 50 ordinary moles
• Fair skin, since fair skin burns much more easily than dark skin
• Personal history or a family history of melanoma
• Weakened immune response—patients who have received drugs following organ transplantation, or patients who have had HIV

But, by far the most common risk factor for developing melanoma is severe blistering sunburns.

So anybody that has—either as a child or as a teenager—been severely burned due to exposure to the sun is at greater risk of developing melanoma. It’s also the same for adults who have been burnt by the sun. In both cases, it is largely due to ultraviolet radiation. One recommendation is to reduce exposure or limit exposure to both natural and synthetic UV radiation because that will increase the risk of melanoma. That’s one of the reasons why you see more people in Texas developing melanoma than those in Minnesota, where the sun is not as strong.

Why is melanoma cancer so deadly?

Melanoma is the most serious form of skin cancer. It’s recognized that if you can diagnose it and treat it early, then it’s completely, or there’s a large chance of it being completely curable. But, if the melanoma advances and spreads to the lymph nodes and other parts of the body, then it becomes very hard to treat and it can become fatal.

When melanoma spreads, one thing that happens is that you can find melanoma cells in the lymph nodes, and these lymph nodes are designed to trap bacteria, cancer cells, and other harmful substances in the lymphatic system. If the cancer has reached the lymph nodes, then there’s a good chance is it has spread to other organs, such as livers, lungs, and brains. When you have the cancer in the liver, lung, and brain, it’s not liver, lung, and brain cancer—it’s still metastatic melanoma and that can be potentially fatal.

How is skin cancer currently treated?

If the diagnosis is melanoma, the first thing to determine what the treatment will be is the extent of the melanoma and that is determined using a process called staging.

• Stage zero—melanoma cells are only on the outer layer of the skin cells and have not invaded deeper tissue.
• Stage one—melanoma hasn’t spread to the lymph nodes.
• Stage two—melanoma is about a millimeter thick, and had not necessarily spread to the lymph nodes.
• Stage three—melanoma has spread to nearby tissue and may have spread to nearby lymph nodes.
• Stage four—melanoma has spread to other organs, lymph nodes, and even skin areas far away from the original tumor.

The treatment you choose depends on the stage of the melanoma.

During surgery, the most common approach for treating melanoma, surgeons remove the tumor and surrounding tissues to make sure no cancer cells are left in the area. The amount removed depends on the thickness of the melanoma and how deeply it’s invaded.

Other approaches that happen simultaneously include:

• Sentinel lymph node biopsy
• Lymph node dissection, where lymph nodes with potential cancer cells—especially ones that are nearby—are removed and assessed to see if cancer is present.

Things that can run simultaneously with the surgery—either before or after—include:

• Adjuvant therapy where a patient can receive GM-CSF
• Cytokines, such as interleukin-2, boosts the immune response, enhancing the recovery process
• Chemotherapy uses drugs are used to kill the cancer cells. These can be provided in a cycle where you have a treatment period followed by a recovery period, then another treatment period. This can be done on an outpatient basis, or a short hospital stay might be needed. Chemotherapy can be provided both through mouth or injection, and even isolated limb perfusion, where you localize it to the limb in question.
• Radiation therapy uses high-energy rays to kill the cancer cells. A large machine directs the radiation at the body and normally it’s a procedure that can be done five days a week for several weeks to control the melanoma, shrink the tumor, and prevent it from spreading to other areas.

Disadvantages to chemotherapy and radiation therapy are there are a number of side effects that are undesirable.

An approach we are focusing on is an aspect of biological therapy called immunotherapy, where we use the body’s natural immune system to recognize the cancer as a problem, attack the melanoma and, respond by using the immune cells to attack it, just the way they would with an infectious disease.

Who is sponsoring this award to work on the development of a skin cancer vaccine?

The American Cancer Society.

Who is with you on the team created to work on this study?

This is a collaborative project with George Weiner, MD, professor of internal medicine and also the director of the Holden Comprehensive Cancer Center. Other investigators include members of my research group and members of Dr. Weiner’s research group, which include Christopher Dahle and Yogita Krishnamachari.

What will the team look or try to develop as part of this study?

We have developed a platform technology that utilizes biodegradable microparticles that have a cocktail of synergistic immunostimulants that, when combined with a marker that is specific for melanoma, will potentially stimulate very, very strong antigen-specific or anti-melanoma-specific immune responses. Our objective will be to optimize the vaccine, characterize the subset of immune cells responsible for this anti-melanoma activity, and carefully monitor any potential side effects; but primarily to develop the strongest, most potent vaccine to stimulate the strongest anti-melanoma activity in a murine melanoma model.

The focus of this study is skin cancer. Can the technique used to develop this vaccine also be used to develop vaccines for other cancers?

Absolutely! What we are developing is a platform technology that stimulates a potent immune response against a melanoma-specific marker or antigen. Because of that, the technology can be readily applied to a wide variety of cancer types by simply changing the target tumor/cancer antigen marker that we are stimulating an immune response against. And obviously every tumor has different challenges and will behave in different ways, but the principle concept can be adapted to a wide variety of cancer types, and that’s one of the positive attributes of the work that we’re currently doing.

This study will last four years. Is there likelihood a vaccine can be developed in that time, or will this study gather information to go forward in the process?

It’s likely that in the first four years we’ll gather enough pre-clinical evidence of the efficacy and safety of this vaccine that we can use that information as a platform for translational clinical studies in future years. It’s worth noting that most of the components that we’re using to build this vaccine have or are likely to receive approval from the FDA, and so the translational potentials are very strong.

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Aliasger Salem, PhD

American Cancer Society

University of Iowa College of Pharmacy

Holden Comprehensive Cancer Center