Potential Power of the Immune System
Immunotherapy, otherwise known as immune therapy or biotherapy, first emerged as a treatment for mesothelioma patients in 2010. Many patients gain access to immunotherapy through clinical trials or ‘compassionate use programs,’ which offer unapproved medications to seriously ill patients outside of clinical trials. When combined with first-line treatment options including surgery and chemotherapy, immunotherapy may alleviate symptoms and improve a patient’s prognosis.
How Does Immunotherapy Work?
Immunotherapy uses a combination of treatments, including cancer vaccines, viruses, and even genetic engineering, to boost the patient’s immune system, the body’s protector against infection and disease, helping it fight off the growth and spread of cancer. When an antigen or unrecognized substance enters the body, the immune system produces specialized proteins called antibodies that attack and destroy that specific antigen. Those specific antibodies will remain inside the body, prepared to defend it against a future attack.
The immune system can’t always detect cancer cells. Sometimes, when healthy cells mutate and spread, the immune system won’t notice. In other situations, the immune system locates the cancer cells but isn’t strong enough to eliminate them.
This is where immunotherapy comes into play. This treatment boosts the immune system and helps the body detect abnormal cells. Doctors use it in one of two ways: to stimulate the immune system into attacking cancerous cells, or inject man-made immune proteins into the area of the body where mesothelioma tumors are growing. In some cases, the proteins are engineered to target cancerous cells.
Immunotherapy Treatment for Mesothelioma
Researchers have developed several types of immunotherapies to attack mesothelioma tumors, some of which are showing promise in clinical trials. Conventional treatments include immune checkpoint inhibitors, cancer vaccines, monoclonal antibodies, cytokines, and adoptive cell transfers.
Key Immune Cells
Researchers target these three types of immune cells when developing immunotherapy treatments.
Dendritic cells – These cells present antigens to B and T cells to trigger a response
- B cells – Sometimes referred to as B-lymphocytes, B cells are a specific type of white blood cell that produces antibodies to destroy antigens.
- Natural killer (NK) cells – A type of white blood cell that attacks infected cells. NK cells recognize cancer cells more efficiently than T cells, resulting in the name “natural killers.”
- T cells – A type of white blood cell that attacks infected cells present in the body, sometimes called T-lymphocytes
Macrophage cells – A type of white blood cell that cleanses the body of unwanted substances, such as dead cells and bacteria, and stimulates other immune cells, like T cells
Passive vs. active immunotherapy
Active immunotherapies boost the immune system, helping it attack cancer cells. Examples of active immunotherapies include:
- Cancer vaccines
- CAR T-cell therapy
Passive immunotherapies enhance anti-tumor responses that already exist in the body. Passive immunotherapy includes:
- Monoclonal antibodies
These antibodies (mAbs) are created in a lab and are designed to reinforce the body’s natural defenses to specific antigens. This area of study is quite new, and researchers are still working to identify specific antigens associated with mesothelioma. So far, the Food and Drug Administration (FDA) has approved more than a dozen man-made antibodies. Several more are currently being tested in clinical trials.
Immune checkpoint inhibitors
The immune system uses specific molecules called checkpoints to differentiate between normal and abnormal cells. These molecules are either activated or inactivated. If a cell is healthy and functioning well, it triggers the appropriate immune response. However, some cancer cells use these checkpoints to sneak under the radar and evade an immune system attack. Immune checkpoint inhibitors are medications made of antibodies that target these checkpoints. These drugs expose cancer cells, allowing the immune system to detect and attack them.
One particular checkpoint is protein researchers call PD-1, which is found on T cells. PD-1 works by preventing T cells from attacking other healthy cells within the body. When it attaches to another protein, called PD-L1, it stops working and tells the defender immune cells not to attack. Checkpoint inhibitor medications like Opdivo, Keytruda, and Tecentriq bind to both PD-1 and PD-L1 cells and prevent them from latching on to each other. If these two proteins can’t attach, T cells in the immune system may be able to recognize and attack abnormal cells.
The FDA has already approved Opdivo, and Keytruda is currently part of several clinical trials with promising results. Researchers do have some concern that in some patients, these drugs could trigger the immune system to attack normal organs in the body. More studies are needed to test the safety and efficacy of checkpoint inhibitors.
Many people are familiar with the word ‘vaccine,’ or an injection given to prevent common diseases like polio, measles, and influenza. Researchers are now applying this same method to prevent certain cancers, like mesothelioma. Cancer vaccines, which are comprised of either cancer cells or pure antigens, are injected into the body. The goal is to boost the immune system’s response to these dangerous cells. However, there is one key difference: measles and polio vaccines are preventative and stop the development of the disease. Cancer vaccinations train the immune system to attack an existing disease.
The MD Anderson Cancer Center in Houston, TX, is currently testing a vaccine as a possible treatment for mesothelioma. It’s called the Wilms Tumor 1 (WT1) vaccine and is the subject of a Phase 2 clinical trial. The study combines WT1 with two other antigens, Montanide and GM-CSF, which boost the growth of white blood cells and increase the body’s immune response. Researchers believe this vaccine could prevent or delay the growth of mesothelioma tumors.
So far, the results are promising. Patients who received an injection of the vaccine survived an average of 21.4 months, compared to patients in the placebo group, who lived an average of 16.6 months. However, more research is needed.
Adoptive cell transfer
Adoptive cell transfer (ACT) involves collecting T cells from mesothelioma patients and using them to grow additional immune cells. The modified T cells are then re-infused or injected back into the body, helping it recognize and attack cancer cells.
Chimeric antigen receptors (CARs) are one successful example of adoptive T cell transfer. CAR T-cells are used to help identify and attach to specific antigens, increasing T cell function and shrinking tumors. Several clinical trials are testing this process on mesothelioma patients.
Cytokines are an immune system protein that boosts the body’s immune response, helping it destroy cancer cells or shrink tumors. Interferon and Interleukin-2 are used to help treat mesothelioma. These proteins create additional ‘attack’ cells in the immune system and assist the body to detect abnormal cells.
Benefits of Immunotherapy for Mesothelioma
The field of immunotherapy continues to grow, and some researchers are calling it the future of cancer treatment. This type of therapy helps destroy existing cancer cells while boosting the patient’s immune system. Immunotherapy has fewer side effects than traditional treatments like chemotherapy and radiation. More research is needed but so far, these immune-boosting treatments are showing promise for mesothelioma patients.
“It’s taken more than ten years, and this is something we never thought would never come to fruition. Now, immunotherapy is first-line therapy. This is just one way of manipulating the immune system to fight cancer. Immunology is here to stay. We’re trying to determine other ways to harness the immune system to help the body fight cancers like mesothelioma.”
~Daniel H. Sterman, MD, Director of the Multidisciplinary Pulmonary Oncology Program at NYU’s Langone Health.