Immunotherapy for Melanoma

Immunotherapy, in general, is a treatment process that uses some medications to activate an individual's own immune system to effectively recognize and kill cancer cells. Immunotherapy for melanoma is based on the principle that a person’s own immune system is able to generate an immune response against the tumor cells. Melanomas are believed to be the most immunogenic tumors and would require a perfect model of immune-based therapies.

Melanoma immunotherapy includes a number of different methods such as vaccine-utilizing antibodies, cytokine-mediated dendritic cells, and whole-cell tumor vaccines. The investigation of vaccines for advanced or metastatic melanoma is still in process.

Below are the types of immunotherapy that are used to treat melanoma:

CTLA-4 Inhibitor

A drug known as ipilimumab helps boost an immune response. However, in melanoma immunotherapy, the drug has a different target. It acts as an inhibitor of CTLA-4, a protein that is present in the T cells. CTLA-4 helps keep the T cells in check. Ipilimumab is intravenously administered once every 3 weeks for only 4 treatments. This drug has helped people with melanomas that cannot be surgically removed to live a longer life. It has also helped those who have metastatic melanomas to live longer. However, the drug has not yet been proven to completely cure melanoma.

Side effects

The common side effects you are likely to have after treatment with ipilimumab include a skin rash, fatigue, diarrhea, and itching. The drug can also cause the immune system to attack other parts of the body that are not targeted during the therapy. This side effect can lead to serious complications in the liver, nerves, skin, hormone-making glands, and eyes, among other organs. In many people, such side effects can become life-threatening. You should report any of the above side effects to your doctor during and after treatment. If you happen to have serious side effects, you should immediately stop the drugs and take such drugs with a high dosage of corticosteroids to suppress the immune system.

Immune Checkpoint Inhibitors

These drugs are new in the market and have shown promising results in the treatment of metastatic melanoma. The big advantage with these drugs is that they have the ability to keep themselves from attacking normal and untargeted cells. To make sure this is achieved, the drug uses “checkpoints”.  The checkpoints are proteins in the immune system that can be turned on and off to begin an immune response. Melanoma cells use these checkpoint proteins to avoid being attacked by the immune system. Therefore, these drugs target the checkpoint proteins and block them, thereby helping the body restore its immune system response against melanoma cells.

PD-1 Inhibitors

Nivolumab and pembrolizumab are examples of PD-1 inhibitor drugs. They are immunotherapy drugs that target the PD-1 protein on the T cells. PD-1 cells are proteins that prevent T cells from attacking other cells in the body. By blocking these proteins, the drugs boost the immune system's response against melanoma cells. PD-1 inhibitors can block the growth of melanoma cells, make the cells shrink, and help people with this type of cancer live a longer life.

PD-1 inhibitors are intravenously administered every 2 to 3 weeks.

Side effects

The common side effects of PD-1 inhibitors include:

• nausea
• diarrhea
• fatigue
• loss of appetite
• itchy skin
• skin rash
• pain in the joints
• bloating

Other potential and serious side effects with PD-1 inhibitors are less often experienced. The PD-1 inhibitors work by removing the brakes from the body's immune system. There are times when the immune system attacks other body parts that are not cancerous, which can cause serious and life-threatening conditions such as problems in the lungs, liver, intestines, kidney, glands that make hormones, and other organs.

It is very important to immediately discuss any of the above side effects with your doctor if they begin to manifest. If you happen to have serious side effects, then you need to stop taking the drugs and get rid of them by taking high doses of corticosteroids to suppress the immune system.

Oncolytic Virus Therapy

Viruses are microorganisms that can kill cells by infecting them. Some of these viruses can be manipulated in the lab so that they are able to only infect and kill cancer cells. These viruses are called oncolytic viruses. Apart from directly killing the cancer cells, the oncolytic viruses can also alert the immune system to attack and destroy cancer cells.

Talimogene laherparepvec, also known as T-VEC, is one good example of an oncolytic virus. It can be used to treat cancer that cannot be removed through surgery such as skin melanomas and cancer that has invaded the lymph nodes. This kind of treatment is administered by directly injecting the virus into the tumors every two weeks. This oncolytic virus is sometimes used to shrink skin tumors. However, it has not yet been proven to shrink cancer growths in other parts of the body. It is still uncertain if this treatment can help increase the life expectancy of melanoma patients.

Side effects

Some potential side effects after the injection of T-VEC include pain at the site of injection and flu-like symptoms.

Cytokines

Cytokines are protein chemicals in the body that are aimed to boost the body's immune system. The two major types of cytokines include interferon-alpha (IFN- α) and interleukin-2 (IL-2). Man-made IFN- α and IL-2 can sometimes be used for patients with melanoma. They are intravenously injected at least for the first time and then given to the patient’s caregivers to give the injections at home.

Imiquimod Cream

Imiquimod is a drug that is applied to the skin and is in cream form. It helps stimulate the immune system's response against skin melanoma. It can be used to kill early stage melanoma cells, which cannot be removed through surgery. It can also be used to treat melanomas that have spread to the skin. The cream is applied 2-5 times a week for about a month. This type of immunotherapy is not used for advanced melanomas.

Bacille Calmette-Guerin (BCG) Vaccine

BCG is a microorganism that is related to the germ that causes tuberculosis. BCG cannot cause any disease in the body. That is why it can be used to stimulate or activate the immune system. The BCG vaccine can be used to treat stage III melanomas by just directly injecting it into the tumors.

Bottom Line

Immunotherapy for melanoma comprises a number of different strategies that utilize whole tumor cells, antibodies, cytokine-mediated dendritic cells, and peptides. Scientists are still investigating vaccines that can be used for the treatment of metastatic (stage IV) melanoma.