Introduction:
Melanoma is a skin cancer that occurs more often in people with weakened immune systems. Lymphocyte is a type of white blood cell present in large amounts in melanoma tumors. These lymphocytes are capable of identifying specific proteins in melanoma cells, and research indicates that immunotherapy is an effective treatment option for melanoma. Immunotherapy works by utilizing the immune system's ability to recognize melanoma cells. Nonetheless, there are potential risks associated with immunotherapy, such as immune-related adverse events, which can result in inflammation in specific tissues.
What Is Metastatic Melanoma?
Metastatic melanoma is one type of skin cancer that has spread beyond the initial site where it first developed and has invaded or metastasized to other body parts. Melanoma cells can spread to the lungs, liver, brain, or bones through the lymphatic system or bloodstream when they separate from the main tumor. Because it has spread and may be found in several different places across the body, metastatic melanoma is sometimes more challenging to treat than early-stage melanoma.
What Is Immunotherapy?
Immunotherapy is a treatment approach that employs the body’s immune mechanisms to fight against diseases, including cancer. The principle of immunotherapy takes into account the ability of the immune system to identify and destroy viruses or bacteria, as well as cancer cells. Thus, immunotherapy works by stimulating the immune system to recognize and attack cancer cells more effectively. This can be done in various ways, such as by using drugs that activate immune cells or by removing immune cells from a patient's body, genetically modifying them to target cancer cells better, and reintroducing them into the patient's system.
What Are the Types of Immunotherapy Used in the Treatment of Metastatic Melanoma?
Immunotherapy has evolved into a promising therapeutic approach in the treatment of metastatic melanoma. Immunotherapy for melanoma is broadly divided into four categories, as listed:
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Adoptive cell therapy.
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Checkpoint blockers.
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Vaccination strategies.
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Biological immunotherapy.
1. Adoptive Cell Therapy:
Adoptive cell therapy (ACT) is a promising treatment approach used in the treatment of metastatic melanoma, a type of skin cancer that has spread to other parts of the body. Utilizing the patient's own immune system to combat cancer cells is a key component of ACT.
Immune cells, in particular T cells, are first isolated from the patient's blood or tumor as part of the ACT procedure. Then, to improve their capacity to identify and combat cancer cells, these T cells are amplified and altered in the lab. Treatment of metastatic melanoma with ACT has demonstrated great efficacy. Complete and long-lasting responses have occasionally been seen, leading to long-term remission. But ACT's effectiveness can differ from patient to patient, and it might not be appropriate for everyone.
2. Checkpoint Blockers:
The immune system has natural checkpoints in place to prevent from attacking healthy cells in the body. Some cancer cells, however, can take advantage of these checkpoints to evade the immune system's recognition and eradication. Specific immunological or cancer cell proteins that control these checkpoints and stop the immune system from attacking cancer cells are the targets of checkpoint inhibitors. Thus, they function by "releasing the brakes" on the body's immune system and help the body's defenses better detect and combat cancer cells.
The major checkpoint inhibitors used in the treatment of metastatic melanoma are listed below:
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Atezolizumab: Atezolizumab is a checkpoint inhibitor that targets the protein PD-L1, which is expressed in some cancer cells and immune cells. It helps the immune system identify and combat cancer cells by inhibiting PD-L1. Advanced melanoma is treated with Atezolizumab in conjunction with other medications, such as Bevacizumab.
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Ipilimumab: Ipilimumab targets the protein CTLA-4, which is expressed in immune cells. By blocking CTLA-4, Ipilimumab activates the immune system to attack cancer cells.
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Nivolumab: It is a checkpoint inhibitor that targets the protein PD-1, which is expressed in some immune cells. By blocking PD-1, Nivolumab enables the immune system to recognize and attack cancer cells. Nivolumab is used alone or in combination with other drugs, such as Ipilimumab, to treat advanced melanoma.
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Pembrolizumab: It is a checkpoint inhibitor that also targets the protein PD-1. Pembrolizumab enables the immune system to recognize and attack cancer cells.
3. Vaccination Strategies:
Vaccines targeting melanoma cells involve using the patient's or donor's own melanoma cells obtained from surgically removed tumors. Dendritic cell-based vaccines utilize antigen-presenting cells with the ability to induce T cell immunity and proinflammatory responses, but their efficacy is limited due to the immunosuppressive nature of the tumor microenvironment. Cancer-causing viruses, such as adenovirus, herpes simplex virus (HSV), reovirus, retrovirus, vesicular stomatitis virus, and measles virus, are being developed as vaccines that can infect cells and stimulate the immune response against tumors. These viruses have shown promising results in preclinical studies and phase I clinical trials regarding safety and efficacy. DNA-based vaccines have been found to be safe and capable of inducing an immune response in clinical trials, but their effectiveness in treating melanoma has been less satisfactory so far.
4. Biological Immunotherapy:
Biological immunotherapy was the first used in the treatment of metastatic melanoma to replace or complete the action of chemotherapy. The most common medications used in biological immunotherapy are higher doses of interleukin 2 (IL-2) and interferons.
Biological immunotherapy is often used in combination with stereotactic radiotherapy, vaccines, or anti-CTLA-4 antibodies. However, such combined approaches have not been validated yet, and only single-agent use is approved except in clinical trials.
Conclusion:
Immunotherapy has revolutionized the treatment of metastatic melanoma, offering new hope for patients facing this aggressive form of skin cancer. Checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 antibodies, have demonstrated remarkable efficacy by unleashing the immune system's ability to recognize and eliminate cancer cells. While barriers, including resistance mechanisms and other side effects, still exist, continuing research is working to optimize and enhance immunotherapeutic strategies for metastatic melanoma. Overall, immunotherapy is a big step forward in the fight against this cruel illness, giving patients new chances for long-term remission and a higher standard of living.
