Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that affects the lining of the lungs and chest wall. It is caused by exposure to asbestos, and its treatment options are limited. One potential avenue for MPM treatment is the use of immunomodulatory agents, which are drugs that help to modify the immune system’s response to cancer cells. In this answer, we will explore some of the immunomodulatory agents that have been used in MPM treatment and their mechanisms of action.
Checkpoint inhibitors
Checkpoint inhibitors are a class of immunomodulatory drugs that target proteins involved in the regulation of T cell activity. These proteins, known as checkpoint proteins, help to prevent the immune system from attacking healthy cells. However, cancer cells can also use these proteins to evade the immune system. Checkpoint inhibitors work by blocking these proteins, allowing T cells to recognize and attack cancer cells.
Two checkpoint inhibitors, pembrolizumab and nivolumab, have been approved by the US Food and Drug Administration (FDA) for the treatment of MPM. In a phase 1 clinical trial, pembrolizumab was shown to have a response rate of 20% in MPM patients who had previously been treated with chemotherapy. In a phase 2 clinical trial, nivolumab was shown to have a response rate of 18% in MPM patients who had previously been treated with chemotherapy.
Immune checkpoint inhibitors
Immune checkpoint inhibitors are a type of immunotherapy that targets proteins involved in the regulation of T cell activity. These proteins, known as immune checkpoints, help to prevent the immune system from attacking healthy cells. However, cancer cells can also use these checkpoints to evade the immune system. Immune checkpoint inhibitors work by blocking these checkpoints, allowing T cells to recognize and attack cancer cells.
One immune checkpoint inhibitor, durvalumab, has been approved by the FDA for the treatment of MPM. In a phase 2 clinical trial, durvalumab was shown to have a response rate of 10% in MPM patients who had previously been treated with chemotherapy.
Cytokine inhibitors
Cytokines are proteins that play a key role in the immune response. Some cytokines can promote the growth and spread of cancer cells, while others can help to inhibit their growth. Cytokine inhibitors are drugs that target specific cytokines, either by blocking their production or by blocking their receptors.
One cytokine inhibitor, interferon-alpha, has been used in the treatment of MPM. Interferon-alpha is a naturally occurring cytokine that can help to stimulate the immune system’s response to cancer cells. In a phase 2 clinical trial, interferon-alpha was shown to have a response rate of 12% in MPM patients.
Immune stimulants
Immune stimulants are drugs that help to activate the immune system’s response to cancer cells. These drugs can work by increasing the production of cytokines, activating T cells, or by other mechanisms.
One immune stimulant, tremelimumab, has been tested in the treatment of MPM. Tremelimumab is a monoclonal antibody that targets a protein known as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). CTLA-4 is a checkpoint protein that helps to regulate T cell activity. By blocking CTLA-4, tremelimumab can help to activate T cells and enhance the immune system’s response to cancer cells. In a phase 2 clinical trial, tremelimumab was shown to have a response rate of 7% in MPM patients who had previously been treated with chemotherapy.
Cancer vaccines
Cancer vaccines are a type of immunotherapy that work by stimulating the immune system to attack cancer cells. Cancer vaccines can be made from cancer cells or from proteins found on the surface of cancer cells.
One cancer vaccine, CRS-207, has been tested in the treatment of MPM. CRS-207 is a live-attenuated Listeria monocytogenes bacteria that has been modified to express the mesothelin protein, which is overexpressed in MPM cells. By presenting mesothelin to the immune system, CRS-207 can help to stimulate an immune response against MPM cells. In a phase 2 clinical trial, CRS-207 was shown to have a response rate of 14% in MPM patients who had previously been treated with chemotherapy.
In conclusion, immunomodulatory agents are a promising avenue for the treatment of MPM. Checkpoint inhibitors, immune checkpoint inhibitors, cytokine inhibitors, immune stimulants, and cancer vaccines have all been tested in clinical trials with varying degrees of success. Further research is needed to determine the optimal use of these drugs and to identify new immunomodulatory agents that can improve outcomes for MPM patients.
