Mesothelioma gene therapy introduces healthy genetic material into the body.
Gene therapy is only available to mesothelioma patients through clinical trials.
Studies have found success in extending patient life expectancies with the treatment.
Gene therapy has been shown to be an effective treatment option for aging patients.
Mesothelioma gene therapy uses genes from healthy cells to help kill cancerous genes within mesothelioma cancer cells by “turning on” the newly introduced genetic materials. When introduced to the body, the genes cause the mesothelioma cells to produce a protein that prohibits the cancerous cells from replicating. In addition to halting replication, the therapy may cause one of two effects, based on which genetic material is used. The therapy either makes the cancerous cells more susceptible to other therapies or causes cancer cell death. Gene therapy for mesothelioma patients is currently only available through clinical trials.
Types of Gene Therapy for Mesothelioma
There are currently no gene therapies specifically approved for the treatment of mesothelioma patients. However, there has been some success in extending mesothelioma patient survival within gene therapy clinical trials. Three common gene therapies for mesothelioma include angiogenic inhibitors, gene transfer and oncolytic virotherapy.
Angiogenic inhibitors prevent the growth of blood vessels. Without growing and functioning blood vessels, mesothelioma tumors cannot get the blood supply they need to grow. While effective in stopping the formation of new blood vessels, angiogenic inhibitors do not kill the cancer directly. The nature of the drug, which focuses on slowing growth rather than killing cancer, requires a patient to be on the medication for extended periods of time. Angiogenic inhibitors are often given as part of a multimodal treatment plan. There are two forms of angiogenic inhibitors. One attacks the vascular endothelial growth factor (VEGF) and the other attacks the VEGF receptors, both of which are part of the blood vessel production process. Possible treatment side effects vary based on whether the angiogenic inhibitor is targeting VEGF or its receptor.
Side Effects of VEGF targeted Angiogenic Inhibitors
- Blood clots
- Gastrointestinal perforation
- Heart attack
- Protein in the urine
Angiogenesis inhibitors that target VEGF receptors include the above side effects, as well as fatigue, diarrhea, biochemical hypothyroidism (decrease in thyroid hormones), hand-foot syndrome (blistering of hands/feet), cardiac failure and hair changes.
Cancer treatment with gene transfer involves the introduction of genes to cancer cells to either slow tumor growth or kill the cancer. The most successful gene transfer therapy involves the use of suicide genes. These viral or bacterial genes have the ability to convert a non-toxic drug into a cancer-killing drug once inside the tumor. By using these suicide genes, normal healthy tissues are not impacted by the cancer-killing or oncolytic drugs, which decreases side effects. Many patients that undergo gene transfer therapy report no side effects at all. Studies have also shown that use of suicide gene therapy may cause the cancer to be more susceptible to radiation therapy.
Gene transfer may be completed with viral or non-viral vectors. The most common viral vectors include:
- Adenovirus and adeno-associated viruses
- Herpes simplex virus (HSV)
- Vaccinia virus
Non-viral vectors are less commonly used as the impacts of their use are unclear, which causes some concern among those in the cancer research community. Naked DNA is often used if a non-viral vector is desired.
Oncolytic virotherapy uses viruses to attack cancer cells. These viruses either target and kill cancer cells or activate the immune system’s own cancer-killing antibodies, known as T-cells. Studies have shown that oncolytic virotherapy has been beneficial for patients whose cancer has become unresponsive to other more traditional therapies, like radiation or chemotherapy. Viruses used for oncolytic virotherapy include the measles virus, HSV, West Nile and Hepatitis B, among others.
Side effects associated with oncolytic virotherapy are typically mild and resolve shortly after treatment. The most common side effects reported following treatment include flu-like symptoms such as chills, fever, muscle aches and nausea. Less commonly, patients report pain at the injection site. For many patients, the potentially curative effects of oncolytic virotherapy outweigh the possible risks.
Mesothelioma Gene Therapy Success
There are currently no gene therapy medications approved specifically for the treatment of mesothelioma, so the treatment is only available through clinical trials for eligible patients. However, researchers have found some success in treating the rare cancer with the therapy, which may help the treatment become widely available in the future.
Malignant pleural mesothelioma patients have been successfully treated with gene therapy that targets the p53 gene. The p53 gene is known as a tumor suppressor gene, as its job is to code for a protein that prevents tumor growth. For many mesothelioma patients, the p53 pathway is inhibited, allowing mesothelioma cells to grow and spread more easily. Studies have found that patients treated with an adenovirus to restore the p53 pathway resulted in an anti-tumor effect. The therapy was also found to be effective and gentle enough to treat patients who are commonly ineligible for other more traditional treatments, including the elderly and those with later-stage disease. Patients in the later stages may have cancer complications, like pleural effusions, that preclude them from certain treatment modalities.
In addition to the successful treatment of the p53 gene, mesothelioma patients are being treated in clinical trials with CAR-T cell therapy. This type of gene therapy works by altering a patient’s T-cells in a laboratory to attack cancer cells, with the addition of a particular gene that helps bind a certain protein to the cancer cells to create the proper immune response. One such drug called Kymriah is currently in phase 1 clinical trials for mesothelioma treatment. While still in the testing phase for malignant mesothelioma, it is the first gene therapy medication to receive U.S. Food and Drug Administration (FDA) approval. The experimental treatment is currently approved for pediatric and young adult acute lymphoblastic leukemia.
Who Is Eligible for Gene Therapy?
Without FDA approval, malignant mesothelioma patients can only access gene therapy treatments through participation in clinical trials. Each trial has their own specific eligibility requirements, which can include criteria like mesothelioma type, cell type and stage. Patients interested in participating in a mesothelioma clinical trial should talk to their mesothelioma specialists about potential trials they may be eligible for, as well as the risks and benefits of the particular trial. To participate in a trial, the patient will need to get the consent of their doctors. Emerging and experimental treatments, like gene therapy, may be a beneficial addition to treatment for some mesothelioma cancer patients.
Mesothelioma researchers are actively studying gene therapy after preliminary studies have shown promising results using the treatment approach. The hope is gene therapy will receive FDA approval in the future, allowing the treatment to be widely available to all mesothelioma patients.