What is ex vivo gene therapy?
Our bodies are made up of cells, and inside each cell is the DNA that we inherit from our parents. Genes are short sections of our DNA that act as blueprints for making the proteins our body needs to function. Proteins are molecules that do most of the work in cells — everything from determining the color of our eyes to coordinating biological reactions and from supporting tissue structure to protecting us from disease. Sometimes a gene is defective and gives faulty instructions to the body’s cells, which can result in disease.
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Narrator: Our team at Children's Hospital of Philadelphia wants to help you understand ex vivo gene therapy. But before we can get into what ex vivo means, we should start by explaining, what is gene therapy? Gene therapy is a way to treat or prevent disease by using genetic material like DNA. First, the basics.
Our bodies are made up of cells, and inside each cell, is its DNA. DNA is divided into short sections called genes. Genes act as instruction manuals, telling ourselves how to make proteins. Proteins are necessary for our bodies to function. Proteins do important work, like helping us digest food and helping our blood clot when we get a cut.
But sometimes, a gene's instructions for making a protein are not correct. This can cause changes in how a protein works. These incorrect instructions can result in a genetic disease. Gene therapy can deliver new instructions to the body to make proteins that function correctly.
Paulina: My leukemia kept coming back. After receiving ex vivo gene therapy, my body was able to conquer the cancer cells.
Narrator: How does gene therapy work? There are two types of gene therapy, ex vivo and in vivo. In vivo means inside the body. When a child receives in vivo gene therapy, that means they'll get an injection or an infusion to fix defective genes.
Ex vivo means, outside the body. Let's talk more about how ex vivo gene therapy works. For ex vivo gene therapy, we remove a child's cells and modify them in a lab. We can either add a new gene or fix the gene that is causing the disease. The modified cells are then returned to the patient. This can require pre-treatment and an infusion during a hospital stay, or in other cases, it can require a stem cell transplant procedure.
One condition that can be treated with an ex vivo gene therapy is sickle cell disease, which is a blood disease that causes episodes of terrible pain. People with this disease now can receive ex vivo gene therapy that fixes the problem.
Temi: Because I received gene therapy for sickle cell disease, I am living a pain-free life.
Narrator: Gene therapy is changing and saving children's lives, and CHOP has been at the forefront of gene therapy breakthroughs from the start. CHOP was the first in the world to use an ex vivo gene therapy to treat a child with leukemia, and we've pioneered many other groundbreaking discoveries. Our determined researchers are exploring the use of ex vivo gene therapy for all kinds of diseases, so that more children worldwide will have bright futures.
Ex vivo gene therapy occurs when cells are removed from a patient and modified outside the body, in a lab, using specialized approaches like adding a new gene to the cell or fixing a gene in a cell that is causing a disease. The modified — or engineered — cells are then returned to the patient. This often requires a transplant procedure, but the goal is treating or curing a disease.
For children who previously only had a full bone marrow transplant (BMT) as a treatment option, ex vivo gene therapy is a much safer procedure and can make a BMT unnecessary.
The techniques used in ex vivo gene therapy combine cutting-edge technologies that allow us to provide a genetically modified cellular therapy that specifically targets the disorder we want to correct. Only in the last decade has this approach been used to treat blood-related disorders and some neurological diseases. New research is exploring the use of these therapies for even more diseases and conditions that affect children and adults.
There are multiple FDA-approved ex vivo gene therapies for multiple diseases. The goal is for these treatments to cure these diseases.
What is the difference between in vivo gene therapy and ex vivo gene therapy?
Gene therapy can be introduced into the child’s body in two different ways. It can be directly infused into them (which is called in vivo gene therapy), or it can be used to modify cells in a lab that will then be transplanted into the child (called ex vivo gene therapy).
With in vivo gene therapy, corrected genes are given directly to the patient. This can occur through an IV or through local delivery to a specific organ, like the eye. This is called “in vivo” gene therapy because the new gene is introduced to the patient’s cells inside the body via a viral vector.
In ex vivo gene therapy, a patient’s own cells are taken out of their body and new genes are introduced to those cells in a lab. The patient gets their own cells back, only now they have been modified to fight their disease. This is called “ex vivo” gene therapy because the new gene is introduced to the patient’s cells outside the body.
How does ex vivo gene therapy work at CHOP?
Ex vivo gene therapy combines elements of cell therapy and gene therapy. An example of this approach is gene therapy for beta thalassemia.
At CHOP, our Cellular Therapy and Transplant team oversees this entire process.
First, cells are removed from the patient by a process called apheresis, which is done at CHOP. These cells are then sent to a specialized facility where the cells are engineered or “repaired” in a lab to introduce a new gene or correct a faulty gene. Once the modified cells are produced in the lab, and the clinical team determines it is safe for the patient to have the cells infused back into the patient’s body, the cells are returned to CHOP. The patient receives chemotherapy to prepare for the ex vivo gene therapy infusion, and when ready, the Cellular Therapy and Transplant team infuses the patient with the genetically modified cells in a process called transplantation.
The patient remains in the hospital to be cared for by the transplant specialists until their immune system has recovered and it is safe to go home. The time in the hospital is usually five to eight weeks.
Like all medical drugs, ex vivo gene therapy is regulated by the Food and Drug Administration (FDA). The FDA must approve these products for clinical trial or commercial use before they are used to treat patients.
The future of ex vivo gene therapy
Potential future applications of ex vivo gene therapy may go beyond blood and neurological disorders to treat other diseases caused by a genetic defect. Researchers are working to develop therapies to treat a weakened, nonfunctioning or abnormal immune system, some autoimmune diseases, like lupus, and additional genetic disorders, including neurological disorders like leukodystrophies.