CAR T-cell therapy is a new type of immunotherapy for cancer treatment that might benefit mesothelioma patients. Clinical trials represent a unique opportunity for patients who qualify to access innovative medicine with great promise. CAR T-cell therapy modifies a patient’s immune system cells and has already shown good results with bone marrow and blood cancers.
What Is CAR T-Cell Therapy?
While new to mesothelioma treatment, chimeric antigen receptor (CAR) T-cell therapy is not entirely new. It has been used and is already approved for other cancer types, including leukemia in both children and adults.[1]
CAR T-cell therapy has so far been most effective for the treatment of blood cancers. It is also being tested in patients with solid tumors, like mesothelioma.[2]
How Many FDA-Approved CAR T Therapies Are There?
The U.S. Food and Drug Administration (FDA) has approved four different CAR T-cell therapies:[3]
- Abecma (idecabtagene vicleucel)
- Breyanzi (lisocabtagene maraleucel)
- Kymriah (tisagenlecleucel)
- Tecartus (brexucabtagene autoleucel)
- Yescarta (axicabtagene ciloleucel)
What Cancers Is CAR-T Approved for?
The FDA has approved these therapies to treat:[3]
- Acute lymphoblastic leukemia
- B-cell lymphoma
- Follicular lymphoma
- Mantle cell lymphoma
- Multiple myeloma
How Does CAR T-Cell Therapy Work?
Treatment with CAR T-cell therapy requires several steps:[1]
- It begins with taking a patient’s blood and isolating T-cells. These are the cells in the immune system that are mostly responsible for attacking and killing unhealthy cells and pathogens in the body.
- T-cells are then modified outside the body to begin producing a cancer-specific receptor molecule on their cell surfaces. This receptor is the CAR (chimeric antigen receptor). It has been created synthetically and is designed to target and attach to proteins on the surfaces of cancer cells.
- Once the T-cells have been modified with CAR, they are injected back into the patient’s bloodstream.
- They multiply, and the CAR molecules on all these T-cells quickly go to work attaching to and killing cancer cells.
CAR T-Cell Therapy Clinical Trials for Peritoneal Mesothelioma
CAR T-cell therapy has been important in treating childhood leukemia. Oncologists and researchers are now testing the therapy with other types of cancers. Researchers often need to develop a new type of antigen because different cancers produce unique proteins on their cell surfaces.
MaxCyte, a cell-based medicine company, has produced a CAR T-cell therapy that it began testing for the treatment of ovarian cancer and peritoneal mesothelioma in 2018. The therapeutic candidate is known as MCY-M11.[4]
MCY-M11 is designed to target the cancer cell-expressed protein mesothelin, which is common in but not exclusive to mesotheliomas. A phase I trial ended and is no longer recruiting, but in 2020, MaxCyte announced the trial would continue.[5]
This is based on initial results that showed the feasibility of intraperitoneal delivery of the therapy. The results also showed the method was safe and that results for patients were promising and warranted further study.[6]
What makes MCY-M11 different from previous trials with CAR T-cell therapies is that the altered T-cells will not be given intravenously. Patients with peritoneal mesothelioma will have their T-cells injected directly into the abdominal cavity so that they will be placed closer to the site of action.
MaxCyte is also using a new type of system for altering T-cells faster, allowing for quicker turnaround times in treating patients.
CAR T-Cell Therapy Clinical Trials for Pleural Mesothelioma
Studies are also just beginning that will use CAR T-cell therapy for pleural mesothelioma and lung cancer. The Abramson Cancer Center in Philadelphia recently received a large grant from the National Cancer Institute to develop a CAR T-cell therapy for these cancers.[7]
Like the MaxCyte product already being tested in peritoneal patients, this one will target mesothelin proteins. This phase I trial is recruiting qualifying patients with pleural mesothelioma.
Further, results from another phase I trial were reported, showing both safety and efficacy with a mesothelin-targeting CAR T-cell therapy. Researchers observed no CAR T-cell-related safety events while witnessing promising improvement in the disease.[8]
CAR T-Cell Clinical Trials Recruiting Mesothelioma Patients
There are currently a few CAR T-cell clinical trials recruiting mesothelioma patients, including these two:
- Mesothelin-targeted CAR T-cell Therapy in Patients With Mesothelioma. This trial is designed to test the safety of varying doses of mesothelin-targeted CAR T-cells.[9]
- A Study to Evaluate the Safety and Efficacy of A2B694, a Logic-gated CAR T, in Subjects With Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression (EVEREST-2)). This study includes phase I and phase II trials to test a new CAR T-cell product. Patients being recruited include those with mesothelioma.[10]
Upcoming CAR T-Cell Therapy Clinical Trial for Mesothelioma
The FDA recently granted a new CAR T-cell therapy known as SynKIR-110 orphan drug status for mesothelioma. The designation is reserved for rare diseases. It provides drug companies incentives for developing treatments for diseases that otherwise get little attention.
This is great news for mesothelioma patients who now have a chance to benefit from CAR T-cell therapy in an upcoming clinical trial. Beginning in 2023, Researchers will trial SynKIR-110 in qualifying mesothelioma patients. The study will be based at the Hospital of the University of Pennsylvania.[11]
Potential Side Effects of CAR T-Cell Therapy
Participating in a clinical trial is important for patients with challenging cancers like mesothelioma. It gives patients a chance to access otherwise unavailable treatments that may work better than currently approved therapies and allows them to help advance knowledge in treating that disease.
On the other hand, there are risks. Clinical trials are conducted to measure effectiveness and adverse effects.
Some of the side effects of CAR T-cell therapy can be troubling. The most common side effect is a condition called cytokine release syndrome (CRS). CRS causes severe, flu-like symptoms: chills, fever, fatigue, and aches, generally lasting between three and twenty-one days. This response is caused by the rapid response of the immune system. In the worst cases, multiple organ failure can occur, so this is a medical emergency.[2]
Another potential side effect of CAR T-cell therapy is CAR T-cell-related encephalopathy syndrome, also known as immune effector cell-associated neurotoxicity syndrome (ICANS). About five days after treatment is initiated, some patients experience confusion, disorientation, and an inability to talk. This is also a medical emergency and should be reported to your provider.
CAR T-cell therapy holds great promise for patients with all types of cancer. It is already helping children with leukemia and is now being tested on rarer but difficult cancers like mesothelioma. If you are interested in participating in a clinical trial, your doctors can determine if you qualify and help enroll you.
