Immunotherapy is a relatively new treatment option for mesothelioma patients.
Immunotherapy can be considered passive or active depending on type.
There are four main types of immunotherapy used to treat mesothelioma.
Immunotherapy is only available to mesothelioma patients through clinical trials.
Immunotherapy is a relatively new mesothelioma treatment that is currently only available to patients through clinical trials. Cancer immunotherapy works by using the patient’s immune system to target and kill cancer cells. There are four main types of immunotherapy treatments, including immune checkpoint inhibitors, monoclonal antibodies, cancer vaccines and adoptive cell therapy.
Types of Immunotherapy
Immunotherapy treatments can be considered active or passive. The treatment is deemed active or passive based on how it influences the mesothelioma patient’s immune system.
Active vs. Passive Immunotherapy
- Triggers an immune memory for a durable, long-lasting response.
- The immune system is stimulated to target and kill cancer cells.
- Triggers an immediate, temporary immune response, often requiring multiple doses.
- Response is triggered by the introduction of synthetic proteins.
The type of immunotherapy that a mesothelioma patient receives will depend on their individual situation. Oftentimes, immunotherapy is combined with another mesothelioma treatment as part of a multimodal plan, so all treatment side effects must also be taken into account.
Immune Checkpoint Inhibitors
Immune cells have checkpoints, or specific molecules on their surface, that are activated or inactivated to trigger an immune response. The immune cells use these checkpoints to determine whether other cells are normal or foreign.
One checkpoint or molecule is a protein called PD-1. Normal cells have a similar protein, PD-L1. When the immune cells’ PD-1 protein interacts with the normal cells’ PD-L1 protein, the checkpoint is inactivated and the immune cells don’t attack the healthy cells. Some cancer cells have the PD-L1 proteins on their surfaces, which can keep them from being attacked by the body’s immune system.
Checkpoint inhibitors work by boosting the body’s immune response to tumor cells. The inhibitors bind to PD-1 or PD-L1 to keep them from binding to one another, inhibiting the checkpoint and causing the immune cells to attack the cancer cells.
The FDA has approved some immunotherapy drugs like nivolumab (Opdivo), Keytruda (pembrolizumab) and Tecentriq for the treatment of non-small cell lung cancer and other types of cancers, and Keytruda continues to show great promise in treating malignant mesothelioma through clinical trials. In one study, Keytruda was used to treat 25 pleural mesothelioma patients. 13 of the 25 patients were able to achieve stable disease after treatment of the immunotherapy drug with minimal side effects. With such success, Keytruda and mesothelioma have been able to improve prognosis for many patients.
Potential Checkpoint Inhibitors Side Effects
- Loss of appetite
- Low thyroid hormone
- Skin rash
Monoclonal antibodies can be used to treat mesothelioma cancer by targeting specific proteins or processes involved with tumor development, maintenance and progression.
Depending on the aspect of tumor development that they target, monoclonal antibodies work in different ways. For example, bevacizumab (Avastin) blocks the formation of new blood vessels, which support tumor growth and metastasis. This immunotherapy drug has been FDA approved for the treatment of lung cancer and has shown success in mesothelioma clinical trials. The National Comprehensive Cancer Network (NCCN) recently updated its guidelines to include bevacizumab as part of a first-line cancer treatment for unresectable mesothelioma, in combination with chemotherapy. One study found the trimodal therapy could extend survival over 18 months, versus about 16 months with the chemotherapy combination alone.
Potential Monoclonal Antibodies Side Effects
- Low blood pressure
- Skin rashes
Therapeutic Cancer Vaccines
Cancer vaccines work in two different ways, by either helping prevent cancers or by treating cancers. To treat cancer, therapeutic cancer vaccines work by triggering an immune response against tumor-specific antigens.
So far, cancer vaccines for mesothelioma are still in the clinical trial stages like other forms of immunotherapy, though they have shown promise. In one case study using dendritic cell vaccination with chemotherapy, patients with malignant pleural mesothelioma saw an extended life expectancy. The average life expectancy for pleural mesothelioma patients is around 12 months. Of those treated with the immunotherapy and chemotherapy combination, seven patients survived for 24 months or longer and two patients survived at least 50 – 66 months.
Potential Cancer Vaccine Side Effects
- Body aches
- Low blood pressure
Adoptive Cell Therapy
Adoptive cell therapy, or adoptive cell transfer, treats mesothelioma by enhancing the body’s white blood cells (T-cells) to trigger an immune response to attack mesothelioma cells. T-cells are removed from the mesothelioma tumor and analyzed in a lab to determine which cells are most active against the cancer. Once determined, those cells are grown into large quantities over the course of 2 – 8 weeks, before being injected back into the patient. Oftentimes, cancer patients continue to undergo chemotherapy and radiation treatments.
There are many different types of adoptive cell therapy, which are still being tested through mesothelioma clinical trials. One that has shown particular promise is CAR T-cell therapy, or mesothelin-targeted CAR T-cell therapy, demonstrating no toxicity among patients, anti-tumor activity and minimal or easily controlled symptoms. Recent studies have noted success in achieving stable disease when CAR T-cell therapy is then combined with checkpoint inhibitors, also exhibiting minimal side effects.
Potential Adoptive Cell Therapy Side Effects
- Accelerated heart rate
- Low blood pressure
- Shortness of breath
With all immunotherapy having potential treatment side effects, patients must discuss all potential risks and benefits of immunotherapy treatment with their medical care team. It’s important to remember that immunotherapy is still considered an experimental treatment and is only available to mesothelioma patients through clinical trials. As such, there may be additional criteria for the particular study that patients must meet to be eligible to receive the treatment.