01. Overview of Gene Therapy
What Is Gene Therapy for Mesothelioma?
Mesothelioma gene therapy is an experimental therapy sometimes used in mesothelioma treatment.
Gene therapy uses genetic material to combat cancer. A doctor may recommend gene therapy after other established treatments have failed.
Scientists have investigated various gene manipulation methods in mesothelioma. Some approaches start by taking cells from the patient. Researchers change the genetic material in the cells, then return the cells to the patient.
Other gene therapy approaches modify cells without removing them from the patient. This method might inject cancer cells with a gene therapy that makes them die.
One common method for mesothelioma treatment involves training a patient’s immune system to fight cancer. Gene therapy can equip immune cells to recognize and attack tumors. This approach is called CAR T-cell therapy.
Several promising studies have investigated gene therapy for mesothelioma. However, it is still considered experimental. Mesothelioma patients can access gene therapy through clinical trials.
Status of Gene Therapies in the United States
The U.S. Food and Drug Administration (FDA) regulates gene therapies. It has approved a small number of cancer treatments in this category. Approved gene therapy treatments have demonstrated safety and efficacy in clinical trials.
KYMRIAH® (tisagenlecleucel) was one of the earliest gene therapy treatments to gain FDA approval. It is a genetically modified immune cell treatment. KYMRIAH treats select forms of leukemia and lymphoma.
In a clinical study, B-cell lymphoma patients treated with KYMRIAH had a median survival greater than two years.
KYMRIAH’s efficacy demonstrates how helpful gene therapy can be in the fight against cancer. With continued mesothelioma research, gene therapy may become more common for this asbestos-related cancer.
Resources for Mesothelioma Patients
02. How Gene Therapy Works
How Does Gene Therapy Treat Mesothelioma?
All cancers result from defective or missing DNA. DNA stands for deoxyribonucleic acid. It is the genetic blueprint for all cellular functions. Gene therapy attempts to patch or replace faulty DNA that contributes to cancer.
For instance, some forms of mesothelioma have a mutated p53 gene. This piece of DNA is known as a tumor suppressor gene. When p53 works correctly, it can help cells identify and combat their own potentially cancerous behavior. When p53 fails, cells may lose this ability to regulate dangerous behavior, potentially leading to cancer.
Some forms of gene therapy teach the immune system to recognize and fight mesothelioma cells. This approach allows immune cells to help pick up the slack left by a broken p53 gene.
Gene therapy treatments may use one or more different strategies to target cancer cells.
All gene therapy strategies modify the genetic material inside a cell. Researchers use a class of tools called vectors to push the new DNA into a cell. A vector serves as a vehicle to deliver DNA into a cell. Common gene therapy vectors include:
- Microparticles and nanoparticles: Tiny spherical particles can carry genetic material into a cell. This vector may be less likely to cause an immune reaction than others.
- Modified viruses: Scientists can modify viruses so that they carry helpful DNA into a cell. The modification can also keep the virus from causing disease.
Some gene therapy approaches may have an important advantage over traditional treatments. Gene therapy may provide the body with longer-lasting tools to fight cancer. These tools may stick around even after therapy ends. This contrasts with chemotherapy treatments, which only fight cancer during treatment.
03. Types of Mesothelioma Gene Therapy
Types of Gene Therapy for Mesothelioma
Gene modification strategies have created several types of mesothelioma gene therapy. Some approaches use gene therapy on mesothelioma cells directly. Others add new DNA to immune cells, allowing the immune system to fight cancer.
Adding an Immune System-Boosting Gene
One gene therapy strategy gives cancer cells DNA to make an immune-boosting protein. If successful, this could force cancer cells to encourage the immune system to target them. This approach may include the following general steps:
- Scientists introduce the new DNA to tumor cells.
- Tumor cells start producing the protein.
- The protein signals the immune system to attack the cancer cells.
- The immune system may continue attacking cancer cells long after the initial treatment.
At least one mesothelioma gene therapy trial has investigated this strategy.
Adding a Suicide Gene
Suicide gene therapy forces cells to make a substance that triggers the cell to die. Suicide genes may harm cancer cells in the following ways:
- Creating a cell poison: Suicide genes can make cells create a toxic substance. This can kill the cell carrying the suicide gene.
- Interfering with vital processes: Suicide genes can produce substances that interrupt cellular functions. This can trigger events leading to cell death.
Scientists can design suicide gene delivery systems to deposit the gene into cancer cells. This may allow the therapy to combat cancer without affecting healthy cells.
Research into suicide gene therapy for mesothelioma is ongoing.
Adding a Tumor Suppressor Gene
A tumor suppressor gene holds instructions for making a tumor suppressor protein. This type of protein helps control cell growth. It may also defend against cellular changes that lead to cancer. A missing or damaged tumor suppressor gene may give rise to cancer.
Research has linked certain tumor suppressor genes to mesothelioma. These include p53 and BAP1. Scientists have looked into using gene therapy to restore the function of p53.
Research on this method is in its infancy. It is possible that the gene therapy would need to reach every cancer cell to be effective. As such, this tactic may prove difficult to develop as a mesothelioma treatment option.
Introducing an Oncolytic Virus
An oncolytic virus can infect and destroy cancer cells but not healthy cells. Oncolytic viruses can exist naturally. They can also be created in a laboratory.
With this technology, DNA manipulation can happen on two levels. Scientists may alter DNA to create the oncolytic virus. Once administered to a patient, the virus may then cause genetic changes that kill mesothelioma cells.
Oncolytic viruses for mesothelioma may have modifications that help them target cancer cells selectively. These modifications aim to improve the safety and efficacy of the virus.
Researchers have investigated oncolytic viruses for mesothelioma, but more studies are needed. Patients interested in this treatment may be able to access it through a clinical trial.
Making Cancer-Killing CAR T Cells
CAR T cells are an immunotherapy created with gene therapy technologies. Doctors create CAR T cells using gene therapy on the patient’s own T cells. This therapy gives regular T cells a chimeric antigen receptor (CAR), making them CAR T cells. The CAR enables the cells to recognize and attack the patient’s cancer.
One CAR T-cell clinical study has demonstrated this process. Researchers first collected immune cells called T cells from pleural mesothelioma patients. They then used gene therapy involving a modified retrovirus. This virus added new DNA to the T cells.
The new DNA enabled the CAR T cells to target a protein called mesothelin. Mesothelioma cells make a lot of mesothelin. As such, the CAR T cells could recognize and attack mesothelioma tumors.
After completing the modification, doctors returned each patient’s CAR T cells back to them. Patients also received an immunotherapy drug called Keytruda® (pembrolizumab). Keytruda allows the natural immune system to recognize and attack cancer cells.
After receiving CAR T cells and Keytruda, patients had a median survival of 23.9 months.
Nearly 40% of study patients still had CAR T cells in their blood more than 100 days after treatment. One patient still had CAR T cells in their blood 18 months after treatment. This patient survived at least 32 months. These results show gene therapy’s potential to help the body fight cancer long after it is administered.
Despite this success, CAR T-cell therapy is not yet widely available. However, CAR T-cell therapy represents an active area of mesothelioma research.
04. Eligibility for Mesothelioma Gene Therapy
Who Is Eligible for Mesothelioma Gene Therapy?
Currently, mesothelioma patients may only receive gene therapy through a clinical trial. Each trial creates its own eligibility criteria. Trial participation requirements may specify:
- Age or age range
- Cell type
- Stage at diagnosis
- Type of mesothelioma
Mesothelioma trials come in a wide variety. As such, patients of all types and cancer stages may be able to find a trial. Any mesothelioma patient interested in trial participation should discuss it with a doctor. A mesothelioma expert can help the patient choose the best option for their situation.
05. What to Expect
The Mesothelioma Gene Therapy Procedure and Experience
Gene therapy is still a relatively new option for cancer treatment. The treatment process may vary because of multiple factors, including the choice of target cells. For example, if gene therapy will target the patient’s immune cells, the patient may have multiple appointments. At one appointment, a healthcare provider will collect the patient’s cells. At a later appointment, the modified cells can be returned to the patient.
Gene therapies targeting cancer cells inside the patient may involve fewer appointments. Thus, each patient’s gene therapy experience may be unique.
Multimodal treatment plans are common in mesothelioma. Patients may receive gene therapy as part of a combination treatment approach. This may mean undergoing surgery, chemotherapy and/or radiation before or after gene therapy.
The FDA has not yet approved any mesothelioma gene therapies. These approaches are still considered to be experimental treatments. Patients who undergo gene therapy may have a different experience than patients who undergo traditional treatments. Individuals considering this treatment should discuss it with a mesothelioma doctor.
06. Survival in Mesothelioma Gene Therapy
Mesothelioma Survival and Prognosis After Gene Therapy
The best median survival reported for mesothelioma gene therapy is 23.9 months. This comes from a specific treatment that combined genetically modified T cells with an immunotherapy drug. These results may not represent the outcome for other types of gene therapy.
Gene therapy survival can depend on multiple factors. These factors include mesothelioma location, stage, cell type and patient health. Survival may also vary because of differences in the gene therapy itself.
Mesothelioma gene therapy research is ongoing. Future studies may explore other approaches for extending mesothelioma life expectancy.
07. Gene Therapy Side Effects in Mesothelioma
Side Effects and Risks of Gene Therapy for Mesothelioma Patients
All cancer treatments come with potential side effects, including gene therapy. Side effects will vary based upon the details of the gene therapy treatment. One study of gene therapy in mesothelioma reported side effects as fairly common. But mild side effects occurred more frequently than serious ones.
Risks of Gene Therapy for Mesothelioma
Experimental therapies, such as gene therapy, come with some level of risk. Known risks of gene therapies include:
- Cancer: If the new gene is added in the wrong place, it might cause cancer.
- Harming the wrong cells: The gene therapy may affect healthy cells. The cells may sustain damage, potentially causing illness or cancer.
- Immune reaction: The immune system may react to the gene therapy. This may lead to inflammation and possibly organ failure.
- Infection by the original virus: The virus should not be able to make copies of itself. But this property may be lost. If so, the virus might become capable of infecting the patient like a regular virus.
Patients considering mesothelioma gene therapy should discuss it with an oncologist. The doctor can help the patient weigh the benefits and risks for their specific factors.
