Immunotherapy for Mesothelioma

Cancer and the Immune System

The immune system is a complex network of cells, tissues, and organs. It is responsible for defending the body against diseases, infections, and harmful invaders such as bacteria, viruses, and other pathogens. It identifies and destroys anything it recognizes as foreign or harmful. However, cancers like mesothelioma pose a significant challenge to the immune system due to their unique characteristics.

Cancer develops when normal cells undergo genetic mutations, causing them to grow and divide uncontrollably. Over time, these abnormal cells form a mass known as a tumor. In mesothelioma, these tumors typically develop in the lining of the lungs, abdomen, or heart due to prolonged exposure to asbestos.

What makes cancer particularly difficult for the immune system to combat is it originates from the body’s own cells. Since these mutated cells are derived from healthy tissue, they often retain many characteristics of normal cells.

The immune system relies on certain markers, or antigens, to distinguish between known and unknown. Because cancer cells share most of the same markers as healthy cells, the immune system struggles to differentiate between the two. This allows the cancerous cells to go unnoticed and unchecked.

Adding to the challenge, cancer cells can actively suppress the immune system. They release chemical signals that create an environment where immune cells are less effective, or they exploit immune checkpoints — mechanisms the body uses to prevent autoimmune responses (attacking healthy cells instead of foreign invaders) — to avoid being targeted.

As a result, cancers like mesothelioma can grow and spread without significant interference from the immune system. This unchecked growth can lead to metastasis, where cancer spreads to other parts of the body, making the disease more difficult to treat.

Understanding how the immune system interacts with cancer has paved the way for innovative treatments like immunotherapy. These therapies are designed to overcome the immune system’s blind spots, empowering it to recognize and attack cancer cells effectively.

This offers new hope to patients with mesothelioma and other challenging cancers.

Activating the Immune System Against Mesothelioma

Immunotherapy is a type of mesothelioma treatment that activates the immune system to fight cancer. Immunotherapy tells the immune system how to identify mesothelioma cells in the body and distinguish them from healthy cells.

There are a few ways immunotherapy can be used to help the immune system fight mesothelioma. Some examples are:

Checkpoint Inhibitors

Checkpoint inhibitors are a specialized form of immunotherapy that empowers the immune system to better detect and destroy cancer cells. They target specific proteins used by cancer cells to evade the immune response, particularly T cells, which play a central role in defending the body against disease.

Cancer cells exploit natural immune checkpoints — mechanisms the immune system uses to avoid attacking healthy cells — to avoid detection. These checkpoints involve proteins on the surface of T cells and cancer cells. Proteins on cancer cells – such as PD-L1 and B7 – bind to corresponding proteins on T cells, like PD-1 and CTLA-4, effectively “turning off” the T cells’ ability to recognize and attack the cancer.

Examples of checkpoint inhibitors are:

Opdivo, Yervoy, and Keytruda are approved for the treatment of pleural mesothelioma. The others are still in clinical trial testing.

Adoptive Cell Therapy

Adoptive cell therapy is a method of genetically changing cells of the immune system to help them fight cancer. Scientists can alter T cells and other immune system cells to direct them to look for cancer cells.

An example of adoptive cell therapy is CAR T-cell therapy. This type of immunotherapy is called cell and gene therapy. Scientists genetically engineer the patient’s T cells to look for cancer cells carrying a specific protein. For mesothelioma, the CAR T cells are engineered to target the protein mesothelin, which is found on the surface of mesothelioma cells.

The patient’s T cells are collected from their blood and genetically modified in a laboratory to more effectively target the patient’s cancer. These new and improved T cells are multiplied and returned to the patient’s blood to begin attacking the disease.

CAR T-cell therapy has shown remarkable success in treating certain blood cancers, such as leukemia and lymphoma, and researchers are actively exploring its potential for solid tumors like mesothelioma. While it is a complex and resource-intensive treatment, CAR T-cell therapy represents a breakthrough in personalized cancer care, offering hope for patients with aggressive or treatment-resistant cancers like mesothelioma.

CAR T-cell therapy for mesothelioma is in clinical trial testing.

Monoclonal Antibodies

Monoclonal antibodies are a type of immunotherapy that enhances the immune system’s ability to recognize and attack cancer cells by targeting specific proteins. These lab-engineered antibodies are designed to bind to protein receptors found on the surface of cancer cells or immune cells, such as T cells.

By doing so, they serve as a bridge, effectively marking the cancer cells for destruction and facilitating an immune response. In mesothelioma treatment, monoclonal antibodies can also block signals that cancer cells use to grow and spread, or deliver toxic substances directly to the cancer cells.

Examples of monoclonal antibodies for mesothelioma are:

• LMB-100, which targets mesothelin, a protein commonly overexpressed in mesothelioma
• Ramucirumab, which- inhibits the VEGFR-2 protein involved in blood vessel formation, cutting off a tumor’s blood supply
• Anetumab ravtansine, which combines monoclonal antibody with a toxin to specifically kill mesothelin-expressing cancer cells

These therapies are currently being tested in clinical trials and represent a growing area of hope for patients with mesothelioma.

Oncolytic Viruses

Oncolytic viruses are modified versions of viruses – such as the herpes simplex virus – used to infect cancer cells. Oncolytic viruses are engineered to infect only cancer cells while ignoring healthy cells, which keeps patients safe.

By infecting cancer cells, the virus causes the cancer cells to die and release certain proteins, which are called antigens. The release of these antigens acts as a distress signal, alerting the immune system and prompting it to identify and attack other cancer cells bearing the same proteins.

By combining direct tumor destruction with the activation of an anti-cancer immune response, oncolytic viruses represent a dual-action therapy with significant potential. They are being actively researched for various cancers, including mesothelioma, and have shown promise in early clinical trials as a powerful tool in the fight against aggressive tumors.

ONCOS-102 is an example of an oncolytic virus for mesothelioma. It is currently in clinical trial testing.

FDA Approvals of Mesothelioma Immunotherapy

The three mesothelioma immunotherapy drugs with FDA approvals are:

All three are approved by the U.S. Food and Drug Administration (FDA) for unresectable malignant pleural mesothelioma. “Unresectable” is the medical term for when surgery is not an option.

In 2020, the FDA approved Opdivo and Yervoy for mesothelioma for use together. In 2024, the FDA approved Keytruda for mesothelioma in combination with chemotherapy.

Mesothelioma Cancer Centers for Immunotherapy Treatment

Below are examples of mesothelioma cancer centers offering immunotherapy treatment or directing treatment with local treatment facilities:

• Dana-Farber Cancer Institute Brigham and Women’s Hospital (Boston, Massachusetts)
• Dan L. Duncan Comprehensive Cancer Center at Baylor St. Luke’s Hospital (Houston, Texas)
• Mayo Clinic (Rochester, Minnesota)
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine (Baltimore, Maryland)
• Swedish Cancer Institute (Seattle, Washington)