Written by: Devin Golden

CAR T-cell Therapy for Mesothelioma

CAR T-cell therapy is a new type of cancer treatment growing in popularity for different types of cancer. CAR T-cell therapy for mesothelioma shows potential due to the expression of a particular protein by these cancer cells.

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Important Facts About CAR T-cell Therapy for Mesothelioma

  • CAR T cells are engineered versions of your immune system T cells. They're modified to target specific proteins expressed on cancer cells.
  • The target protein for mesothelioma and other cancers, including lung cancer, is mesothelin. This protein is on nearly all mesothelioma tumors.
  • CAR T-cell therapy is still in testing for mesothelioma. Clinical trials are ongoing for this cancer. The FDA has approved six CAR T-cell therapies for different types of blood cancer.

What Is CAR T-cell Therapy?

CAR T-cell therapy is a type of cancer treatment within the field of immunotherapy. More specifically, it’s called targeted cancer therapy. CAR is an acronym for “chimeric antigen receptor.”

Doctors adjust your body’s natural T cells to better fight cancer. This is called an adoptive cell therapy since it treats cancer by changing an element of your immune system cells or the cancer cells. Some people call CAR T-cell therapy a type of cancer cell and gene therapy. Immunotherapy and cell and gene therapy are similar to one another.

CAR T-cell therapy is approved by the U.S. Food and Drug Administration (FDA) for specific types of blood cancer: leukemia, lymphoma and myeloma. It is not approved for mesothelioma, lung cancer or any other solid tumors.

What Are CAR T cells?

CAR T cells are genetically modified versions of your T cells, which are a type of white blood cell called lymphocytes. These cells are tasked with fighting off diseases, such as viruses and cancer. Doctors add a chimeric antigen receptor, or CAR, to extracted T cells to make them more focused on finding and killing cancer tumors.

These cells get a CAR focused on a specific protein, or antigen, expressed by the target cancer. This target protein is a sign that you have this specific cancer. The protein is also a way to direct T cells to prioritize looking for cells expressing this specific antigen.

CAR T cells: A Living Drug and Cancer Vaccine

A benefit of CAR T-cell therapy as a treatment for mesothelioma is that many patients only need one infusion of treatment. A single infusion can work for months or years. CAR T cells can continuously replicate within the immune system and create a “living cancer therapy” for years after the treatment is given.

This essentially becomes a cancer vaccine, as the CAR T cells remain active and populated for years to prevent cancer from returning.

This is a significant difference from standard cancer treatment, such as chemotherapy for mesothelioma and even other forms of immunotherapy for mesothelioma. Since these drugs stop working after a few days or weeks, patients need multiple sessions of treatment to keep cancer at bay.

How to Use CAR T-cells for Mesothelioma

The first step to making CAR T cells is finding a protein to target. It’s easiest if the protein exists on the surface of cancer cells.

Mesothelioma tumors produce a protein called mesothelin on the surface of cells. This protein is expressed on both pleural mesothelioma and peritoneal mesothelioma. CAR T-cell therapy is a possible treatment for both types of mesothelioma.

Dr. Raffitt Hassan, of the National Cancer Institute, wrote a paper in 2007 about targeting mesothelin for cancer immunotherapy. He said mesothelin is expressed in “virtually all” cases of mesothelioma.

Ovarian cancer, colorectal cancer and pancreatic cancer also express mesothelin at times, although not as often as mesothelioma.

History of CAR T-cell Therapy

CAR T-cell therapy emerged at the beginning of the 21st century as a cancer treatment. The concept of cell and gene therapy was not well-funded. However, many scientists still believed in the idea of enhancing the body’s T cells by adding a gene that directed them toward cancer tumors.

Dr. Carl June, of Penn Medicine’s Abramson Cancer Center, was one of the scientists who never gave up on this field of cancer treatment. Dr. June created a CAR T-cell therapy and tested it in clinical trials for various blood cancers, including lymphoma and leukemia. He received funding from non-profit organizations, including Alliance for Cancer Gene Therapy, and proved CAR T cells could treat these diseases.

A few of Dr. June’s patients in his 2010 and 2012 clinical trials have reached a decade or more of survival since getting CAR T-cell treatment. Many news outlets reported at the beginning of 2022 that these patients were “cured” of their cancer thanks to CAR T-cell therapy.

The FDA approved the first CAR T-cell therapy in 2017. Five more have followed with approvals since then.

FDA Approvals of CAR T-cell Therapy

There are six CAR T-cell therapies approved by the FDA. They are approved for various blood cancers and only after patients have tried other treatments unsuccessfully.

The six approved CAR T-cell therapies are listed below with their brand names first and generic scientific name in parenthesis:

1

Kymriah (tisagenlecleucel), approved for patients up to 25 years old with acute lymphoblastic leukemia and all patients with non-Hodgkin lymphoma

2

Yescarta (axicabtagene ciloleucel), approved for non-Hodgkin lymphoma

3

Tecartus (brexucabtagene autoleucel), approved for mantle cell lymphoma

4

Breyanzi (lisocabtagene maraleucel), approved for types of non-Hodgkin lymphoma, including large B-cell lymphoma

5

Abecma (idecabtagene vicleucel), approved for multiple myeloma

6

Carvykti (ciltacabtagene autoleucel), approved for multiple myeloma

Steps for Making CAR T-cells

The process of making CAR T cells usually takes 1-2 weeks, although researchers are trying to shorten the time to help patients. There are multiple steps required to enhance T cells to fight cancer:

1

Doctors remove the patient’s blood, which is where T cells live in the body.

2

The medical team separates T cells from the blood.

3

T cells are sent to a laboratory.

4

Scientists add the CAR gene to the T cells through a viral vector (a non-active virus carrying the gene).

5

Scientists activate the CAR T cells and multiply them in the laboratory, creating copies of the new T cells.

6

The T cells are returned to the medical center.

7

Doctors infuse the CAR T cells back into the patient’s blood system.

CAR T-cell Therapy Survival Rates

The survival rate for CAR T-cell therapy depends on the specific CAR T cell and the type of cancer. Since this therapy is only approved for blood cancers, most of the survival data is limited to those types of tumors.

Yescarta led to a 42% 5-year survival rate for large B-cell lymphoma, which is the most common type of non-Hodgkin lymphoma. Some patients had a complete response – the tumor disappeared – and their 5-year rate was 64%. For a few of those patients, the cancer returned after a couple of years.

Kymriah, which is approved for a type of leukemia affecting kids, had a complete remission rate of 85%. The survival rate for one year was 77%. Kymriah is also approved for non-Hodgkin lymphoma and had a survival rate of 70% at one year.

Tecartus, which is approved for mantle cell lymphoma, helped patients reach a median survival of 46.6 months. Tecartus is also in testing for leukemia, leading to a median survival for 25 months.

Mesothelioma survival rates are poor, so CAR T-cell therapy leading to similar results would be a huge improvement in life expectancy of patients.

CAR T-cell Therapy Side Effects

One of the benefits of CAR T-cell therapy compared to chemotherapy is the low rate of side effects. Some side effects may occur but they don’t usually last for as long as chemotherapy.

Cytokine release syndrome is the most common side effect of CAR T-cell therapy. This condition is an overproduction of cytokine, a chemical in your blood. Producing too much cytokine causes nausea, fever, chills, trouble breathing, headaches, dizziness and fatigue. Patients often experience cytokine release syndrome in the days immediately after getting their CAR T cells.

While the side effect is uncomfortable, it’s proof the therapy is working. CAR T cells are multiplying, which is what causes the cytokine overproduction. The effects are also short-lived and medical teams usually can manage it with medication in the hospital.

Another side effect is central nervous system issues: headaches, confusion, seizures, loss of balance, and trouble speaking. CAR T-cell therapy can lead to low blood cell counts, causing infection or bruising, or low potassium or sodium.

The rate of serious side effects from CAR T cells is low. The most serious one usually ends within a few days of receiving treatment.

CAR T-cell Therapy in Clinical Trials for Mesothelioma

A few ongoing mesothelioma clinical trials feature CAR T cells. A few others have completed with positive survival data.

Memorial Sloan Kettering Cancer Center hosted a phase 1 study of CAR T-cell therapy for mesothelioma and other mesothelin cancers. The trial paired CAR T cells with Keytruda, an immunotherapy drug that blocks the protein PD-L1. Their median survival for 18 patients was 23.9 months.

Penn Medicine and the University of Pennsylvania’s Abramson Cancer Center is hosting a phase 1 trial for a mesothelin-targeted CAR T cell. The trial includes pleural mesothelioma and peritoneal mesothelioma.

Common Questions About Virotherapy for Mesothelioma

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How do CAR T cells treat mesothelioma?

CAR T cells are enhanced versions of your immune system T cells, which are white blood cells tasked with fighting infections, bacteria and other diseases. Cancer can withstand the attacks of T cells or sidestep their guarding of the body’s health. CAR T cells are modified to look for specific protein found on these cancer cells. For malignant mesothelioma, the protein targeted is mesothelin.

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How do you get CAR T-cell therapy?

CAR T-cell therapy for mesothelioma is only available in clinical trials currently. The FDA approved six CAR T-cell treatments for various types of blood cancer, but no CAR T cells have been approved for solid tumors like mesothelioma. Clinical trials are your best option to receive this novel therapy.

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What is the average survival for CAR T-cell therapy?

In clinical trials, CAR T-cell therapy has helped patients improve their mesothelioma life expectancy and survival. For blood cancers, this therapy has led to enormous success. Some patients are living a decade after their treatment. CAR T-cell therapy is different than other treatments because it is often a one-and-done treatment, meaning patients only need a single infusion. The hope is CAR T cells infused into the body replicate and create a living drug for years after the infusion.

Sources & Author

    1. Mesothelin targeted cancer immunotherapy. European Journal of Cancer. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265108/. Accessed: 06/03/2022.
    2. A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease, in combination with the anti-PD-1 agent pembrolizumab. Cancer Discovery. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/34266984/. Accessed: 07/19/2021.
    3. CAR T Cells in Mesothelin Expressing Cancers. Clinicaltrials.gov. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT03054298. Accessed: 06/03/2022.
    4. Cure is a big word. Alliance for Cancer Gene Therapy. Retrieved from: https://acgtfoundation.org/story/june/. Accessed: 06/08/2022.
    5. Approved CAR T-cell therapies for blood cancers. Alliance for Cancer Gene Therapy. Retrieved from: https://acgtfoundation.org/for-patients/approved-car-t-therapies/. Accessed: 06/08/2022.
    6. Yescarta® Is First CAR T-cell Therapy to Report Five-Year Survival Data From Pivotal Study Showing Durable Long-Term Survival in Patients With Refractory Large B-cell Lymphoma. Gilead. Retrieved from: https://www.gilead.com/news-and-press/press-room/press-releases/2021/12/yescarta-is-first-car-t-cell-therapy-to-report-five-year-survival-data-from-pivotal-study-showing-durable-long-term-survival-in-patients-with-refract. Accessed: 06/06/2022.
    7. Kymriah Safely Treats ALL and NHL in Real-World Setting. Cure Today. Retrieved from: https://www.curetoday.com/view/kymriah-safely-treats-all-and-nhl-in-real-world-setting. Accessed: 06/06/2022.
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About the Writer, Devin Golden

Devin Golden is the content writer for Mesothelioma Guide. He produces mesothelioma-related content on various mediums, including the Mesothelioma Guide website and social media channels. Devin's objective is to translate complex information regarding mesothelioma into informative, easily absorbable content to help patients and their loved ones.