Immunotherapy is an emerging type of treatment that uses the body’s own immune system to try to fight and destroy cancer cells to shrink tumors, treat symptoms, and possibly cure cancer. There are various ways to do this, such as strengthening the immune system or adding synthetic immune system components. Some types are referred to as biologic therapy and others involve gene therapy, but all types of this treatment involve the immune system in some way.
For patients living with mesothelioma, immunotherapy may provide an adjuvant treatment to be used in conjunction with surgery, radiation, or chemotherapy. Research and use of this treatment for mesothelioma has helped some patients live longer and find relief from symptoms, but so far there has not been any proof that immunotherapy could cure mesothelioma.
How the Immune System Works
The immune system is the biological system in the body that is responsible for protecting against pathogens like bacteria and viruses. The immune system fights infections, prevents disease, and recycles and removes damaged cells and dead cells. The immune system recognizes some foreign agents in the body, including cancer cells, from birth, but it also develops as a person ages and is exposed to more pathogens, learning to attack new agents.
The immune system includes several types of immune cells, which make and utilize the agents of the immune system. These include antibodies and cytokines. Antibodies are proteins that recognize antigens, compounds on the surfaces of infectious agents. By recognizing antigens, they can signal the immune system to attack a pathogen. Cytokines are also proteins and they work to coordinate the immune response. Lymphocytes are cells of the immune system: B cells produce antigens and T cells produce cytokines and clean up dead and diseased cells. Macrophages are large immune system cells that consume dead cells and cellular debris.
The immune system is essential for survival, but it is complicated and imperfect. For example, the immune system in some people—for reasons not understood—attacks and damages healthy tissue. When this happens a person is said to have an autoimmune disorder. Examples include rheumatoid arthritis, in which the immune system attacks joints, and multiple sclerosis, which affects the protective tissue around nerves.
What is Immunotherapy?
Immunotherapy to treat cancer is a treatment strategy that uses the immune system in the body to fight cancer cells. There are two main ways this is done: stimulating the immune system in some way to make it work harder or to specifically attack cancer cells and adding in immune system components to instigate an attack on the cancer cells. The treatment may be general, and boost the actions of the immune system overall, or it may be specific, encouraging the immune cells to go after one type of cancer cell.
Antibodies are the proteins the immune system produces that circulate the body, attaching to antigens when they find them. Once attached to the antigens on a pathogen, the antibodies recruit other cells to fight the invader. Antibodies can be created in the lab to specifically target an antigen. For cancer treatment, if researchers know what the antigen on the cancer cell is, they can design an antibody and use that to trigger the immune system to attack the cancer cells. The antibodies created in this way are known as monoclonal antibodies.
Monoclonal antibodies work better for some types of cancer than others. It is important that an antigen can be identified, but this isn’t always easy, depending on the type of cancer. For mesothelioma, an antigen that can be targeted is called mesothelin. Using monoclonal antibodies is not a cure for mesothelioma, but they can be used along with other treatments, like surgery. The strategy may be more effective for some patients than others.
Vaccines are manipulated pathogens, like viruses, that are given to people to prevent illness. For instance, millions of people get the flu vaccine each year. It uses inactivated flu viruses to stimulate the immune system so that it learns to recognize and attack the active flu virus and prevent an infection. Cancer vaccines are similar and are used to stimulate the immune system to attack cancer cells to either actively treat the cancer or prevent regrowth of tumors after remission.
Immune Checkpoint Modulators
The immune system should be able to tell the difference between pathogens and healthy cells so that it only attacks the former. To distinguish between the two, there are molecules on immune cells that have to be activated in order for them to attack pathogens. Cancer cells can develop molecular strategies for getting around these so-called checkpoints to avoid being attacked by immune cells. One emerging immunotherapy strategy is to target the checkpoints with specially-designed drugs. One of these, called atezolizumab, has been successful in treating lung cancer.
A passive approach to immunotherapy involves using strategies to boost the immune system, but without specificity. This is also sometimes called non-specific immunotherapy. These strategies may be used alone, with other types of immunotherapy, such as with cancer vaccines, or with other types of cancer treatments.
One passive strategy is to inject the body with cytokines, the proteins in the immune system that promote the growth and development of immune cells. There are also synthetic drugs that can be used to boost the immune system, although how they do so is not fully understood.
There is also a type of bacterium that can be used to boost the immune response. BCG, or Bacille Calmette-Guérin, is commonly used in bladder cancer and skin cancer. A solution of the bacteria is injected into the bladder or the tumor and the cells attract the immune cells, which then attack the cancer cells. BCG does not cause infections in people, although it will stimulate inflammatory symptoms, similar to flu symptoms.
BCG has been tested in mesothelioma patients. In one study the treatment helped to prevent pleural effusions, the buildup of fluid in the chest cavity. Another study in which mesothelioma patients who had undergone a thoracotomy received regular injections of BCG after the surgery, demonstrated that this treatment could reduce symptoms significantly.
Immunotherapy for Mesothelioma
Using immunotherapy to treat mesothelioma has been tricky. Targeting antigens, for instance has been difficult because mesothelioma cells seem to produce few antigens. Mesothelin is one of the few recognized, and against which monoclonal antibodies can be used, but it is not produced in all cases of mesothelioma. BCG showed some success in early studies, but has not become a regular treatment for mesothelioma.
Immunotherapy continues to be a promising line of treatment and research and ongoing studies should lead to developments that help more patients with cancer, including those with mesothelioma. Boosting the immune system in patients with mesothelioma does seem to have some impact on patient outcome, but it often needs to be used with other treatments to have a positive effect. As research continues, more advances should be found to give patients hope and greater comfort as they fight mesothelioma.
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