Mesothelioma and Immunotherapy
Immunotherapy is an experimental form of cancer treatment. People with mesothelioma can have access to it, but only as a clinical trial. The first clinical trials started in the 1980s and different tactics have been tried since with varying results. If used together with radiotherapy, chemotherapy, and/or surgery, immunotherapy is able to enhance the prognosis, as well as improve the patient’s quality of life. This is because it helps to boost the overall immune system and its function. It does not, however, cure cancer.
Immunotherapy in Action
Immunotherapy acts by enhancing the performance of the immune system, which is necessary for stopping diseases from developing, and removing dead and damaged cells. The immune response system is either passive or active. The passive element is present when we are born and helps to fight diseases. The active, or adaptive, element grows and develops as we are exposed to viruses, bacteria, and other pathogens throughout our lifetime.
The immune system is made up of three types of immune agents, which are:
- Antigens, which are found on foreign pathogens and stimulate a response from the immune system.
- Antibodies, which are B cells and help to spot and attack any antigens.
- Cytokines, which are T cell proteins that help the immune system fight pathogens, including cancer.
Active Immunotherapy and Mesothelioma
Immunotherapy essentially aims to trigger an immune response by presenting specific antigens. This can be difficult with tumors, as the immune system will only respond to specific antigens, telling it that it is a diseased cell. In mesothelioma, tumors usually grow locally, rather than spreading in the same way that other cancers do. As a result, they are often very large before they spread to the lymph nodes and trigger an immune system response.
The antigen in mesothelioma tumors is mesothelin. Scientists have tested the SS1P protein, which is a synthetic protein that includes the anti-mesothelin antibody. At present, the trials are in phase 1 and appear to be promising. Out of 21 patients that were tested, 19 experienced disease stabilization, and four experienced a partial response.
Another practice that is used as part of immunotherapy is that of injecting live immune cells. This is also in phase 1 at present. Ten patients have been tested, and all had an immune system response.
Passive Immunotherapy and Mesothelioma
A second type of immunotherapy used on mesothelioma patents is known as ‘passive immunotherapy’. This does not trigger a response from the immune system in general, but instead, the patient is injected with immune cells that specifically attack cancers. This means that instant protection against antigens is provided.
Most of the time, passive immunotherapy is done through monoclonal antibody (mAb) therapy, which focuses either on a protein or enzyme inside the cancer cell, or on the surface of the cell, which is the antigen. The antibodies are synthetically produced and get to work on destroying a specific type of antigen. While this sounds revolutionary, which it is, it also has significant limitations:
- It is generally only used if surgery, radiotherapy, and/or chemotherapy has proven to be unsuccessful. Unfortunately, the body is then usually quite weak and this means the mAb therapy may not work.
- mAb targets a specific antigen, and this may not be present in every person. Not every case of mesothelioma is the same. The success rate, therefore, is just 20% to 30%.
- Patients who have already had radiotherapy or chemotherapy may have mutated tumor cells. If so, this will not be recognized by the mAb therapy.
- The therapy is considered very toxic and will make people quite sick.
Phase II clinical trials are currently taking place to study the effects of Amatuximab or MORAb-009. Unfortunately, although there have been some positive results, these have not yet been sufficient to warrant a phase III. This is because the survival rate with Amatuximab is 14.8 months, which is only 2.8 months more than with untreated mesothelioma.
It is also possible for immunotherapy to be classed as ‘non-passive’, which means specific cells are injected to target the disease. This includes cytokines, which help to kill off a cancer cell, or at least stop it from multiplying.
Bacillus Calmette-Guerin and Mesothelioma
In the 1970s, it was found that the Bacillus Calmette-Guerin (BCG) vaccine could help to treat cancer. BCG is made up of live tuberculosis bacteria. It is used to vaccinate against tuberculosis and is also used in the treatment of bladder cancer. Some studies have been done to determine whether it could also be effective for pleural effusions and mesothelioma, injecting patients on a monthly basis. It was shown that the BCG injections could stop fluids from building up in the cavity of the lungs.
Another study was conducted, involving 30 different patients who suffered from mesothelioma. They were first given a thoracotomy to remove cancerous tissue. Then, they were provided with radiotherapy or chemotherapy. After this, they were injected with BCG thrice a week. After six weeks, the interval was lengthed to once a week. Twenty-eight patients said that they had an increased quality of life, and their life expectancy, if they had a light tumor, was increased to 21.5 months. After six years, one patient was still alive.
It is currently not offered as a mesothelioma treatment, however. This is mainly because other clinical studies have shown that the effect of mycobacteria have not been sufficient to warrant phase III trials.
Where Will Immunotherapy Go Next?
It is believed that development of immunotherapy will improve treatment options for mesothelioma and, perhaps, increase prognosis, particularly if it is used as part of another therapy. Presently, it seems that mixing immunotherapy with chemotherapy marginally increases survival rates. However, further studies are needed.
What has been discovered is that mesothelioma prognosis and penetrating lymphocytes are correlated. This means that for those patients who have a better immune response, their survival rate may also increase. At the same time, studies are being conducted into asbestos itself, and it has been found that immune cells exposed to asbestos caused the production of cytokines that permitted an increase in mesothelioma cells in humans. This could mean that an immunotherapy that kills the immune cells could also be beneficial in terms of survival rates.