Mesothelioma Gene Therapy

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This page was medically reviewed by James Stevenson, M.D. on April 19, 2019. For information on our content creation and review process read our editorial guidelines. If you notice an error or have comments or questions on our content please contact us.

James Stevenson, M.D. Thoracic Medical Oncologist

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Mesothelioma gene therapy is an emerging treatment type that is currently available to patients through participation in clinical trials. Gene therapy treats the disease through the introduction of new cells to kill cancer cells, or enable more effective use of other treatment types.

01. Types of Gene Therapy

Types of Gene Therapy

There are currently many types of gene therapy in clinical trials at cancer centers across the world. Each gene therapy clinical trial is focused on treating specific cancer types and identifying which gene therapy modality is best suited for that particular cancer. Of the many trials in progress, only a handful of gene therapy approaches have achieved success in extending patient life expectancies.

Gene Transfer

Gene transfer introduces genes to the cancer cells to slow growth of tumors or kill cancer cells. The most common gene transfer is through the use of “suicide genes.” These genes convert a non-toxic drug into an oncolytic (cancer killing) drug once inside the tumors. Suicide gene therapy may be administered using non-viral or viral vectors, including retroviruses, vaccinia virus, lentivirus and adenovirus. Suicide gene transfer therapy, either through use of viral or non-viral vectors, has been successful in treating chemotherapy-resistant cancers and can improve the effects of radiation therapy. Because the cancer-killing drug is only administered within the tumor, patients have been able to receive this treatment with no side effects.

Oncolytic Virotherapy

Oncolytic virotherapy is a cancer treatment that uses a virus to break down mesothelioma cells while leaving healthy cells unharmed. Viruses being used for this specific gene therapy include measles, herpes simplex virus (HSV), west nile and hepatitis B, among others. Weakening cancer cells with oncolytic virotherapy may increase the efficacy of adjuvant therapies like chemotherapy and radiation therapy. When a combination of these therapies are used, the cancer may be eliminated. The side effects related to oncolytic virotherapy are generally mild and dissipate a few days after treatment.

Side Effects of Oncolytic Virotherapy
  • Chills
  • Fever
  • Loss of appetite
  • Muscle aches
  • Nausea
  • Pain at injection site
02. Gene Therapy Treatment

How Gene Therapy Treats Mesothelioma

Many clinical trials continue to test different forms of gene therapy for mesothelioma. For pleural mesothelioma patients, which is the most common form of the cancer, studies have found success using gene therapy to create an anti-tumor effect through targeting the mesothelioma-associated defective genes. For many cancers, including pleural mesothelioma, researchers have noted a defect in the p53 gene, which codes a protein responsible for regulating normal cell function. Without a properly functioning p53 gene pathway, the cancer cells become immune to apoptotic cell death. One preclinical trial used an adenovirus vector to revive the p53 pathway and achieve apoptosis of the cancers cells, which resulted in tumor regression. Additionally, this favorable result was achieved on patient populations that may be ineligible for other treatment modalities, such as elderly patients and those with pleural effusions, which typically indicate a later stage of disease.

CAR-T cell therapy has also been used to treat mesothelioma patients. The form of treatment is the first gene therapy medication to receive FDA approval for select cancers, including pediatric and young adult acute lymphoblastic leukemia. The drug is currently in a phase 1 trial to test its efficacy in treating mesothelioma. This gene therapy approach uses the body’s immune system, like an immunotherapy drug, as the patient’s own cells (T-cells, a type of white blood cell) to attack the cancer cells after they have been genetically modified to identify cells that have mesothelioma marker proteins, such as mesothelin. The trial is too early for conclusive results, but the combination of two emerging treatments, gene therapy and immunotherapy, is promising for mesothelioma patients in need of viable treatment options.

03. Gene Therapy Eligibility

Eligibility for Mesothelioma Gene Therapy

Mesothelioma patients may only receive gene therapy if they are accepted into a clinical trial. Clinical trials create their own eligibility criteria, which can include type of mesothelioma, stage and cell type. The wide variety of trials may enable patients of all stages of mesothelioma to be eligible and participate in a trial if they so desire.

To participate in clinical trials, patients must provide consent to their doctors. A patient’s healthcare team will be able to discuss potential benefits of the trial for that patient’s specific case of mesothelioma.

Patients should also make sure to ask questions about any risks of the emerging treatment, as well as what other treatments or clinical trials may be viable for their individual case.

04. Side Effects and Risks

Side Effects and Risks of Gene Therapy

The side effects of gene therapy vary based on which type of gene therapy is being administered, including chills, fever and fatigue. While varied, side effects endured during gene therapy are typically mild and often not long lasting. However, with further research through clinical trials, doctors will have a better understanding of the efficacy of the treatment and any other potential risks that may emerge.

Gene therapy may be a favorable treatment option for cancer patients whose disease has not responded to other treatment modalities. Patients should discuss potential risks and side effects with their mesothelioma specialist and the doctors performing the gene therapy clinical trial before beginning treatment.

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