Medically reviewed by David A. Williams, MD
Gene therapy is a way of treating or preventing disease by altering the genetic instructions within an individual’s cells. Genes are responsible for virtually every aspect of cell life: they hold the code for proteins that enable cells to grow, function, and divide. When a gene is defective, it can give rise to proteins that are unable to do their job. When a gene is missing, or is overactive, important bodily functions may be impaired. The goal of gene therapy is to correct such problems by fixing them at the source.
Gene therapy can involve replacing abnormal or absent genes with healthy ones that enable cells to produce useful proteins. It also can involve changing the way genes are regulated, so that under- or overactive genes operate properly. Finally, gene therapy can be used to express entirely foreign genes in cells that alter their function and/or survival.
A variety of efforts are underway to apply gene therapy to cancer treatment. Most are in early, exploratory stages, where they’re being studied in the laboratory or in clinical research trials. One approach, however, known as CAR T-cell therapy, has received approval from the U.S. Food and Drug Administration for use as a therapy in certain groups of patients and is expected to receive additional approvals in the near future.
Research in gene therapy for cancer is currently focused in multiple areas, including genetically engineered viruses that directly kill cancer cells, gene transfer to alter the abnormal functioning of cancer cells, and immunotherapy (which includes CAR T-cell therapy), which helps the immune system better find and kill tumor cells.
Genetically Engineered Viruses
This approach uses specially modified viruses (called oncolytic viruses) that target and destroy cancer cells while leaving normal cells unharmed. The viruses, engineered to contain certain genes, are designed to infect cancer cells and, once inside, to produce proteins that cause the cells to die.
In animal studies, such viruses have achieved promising results in a variety of cancers, including colon, bladder, and osteosarcoma (a form of bone cancer). One of the challenges in adapting this approach for human patients is that most people have antibodies to several of the types of viruses used in the animal studies. As a result, the immune system is often able to clear the viral agent before it has had a chance to infect cancer cells. Researchers have responded by using other types of viruses for trials in humans.
In trials using a type of virus known as adenovirus, viral therapy has shown encouraging results against several types of cancers, including squamous cell cancers of the head and neck, and is being tested as a preventive treatment for precancerous oral tissue. Trials involving modified forms of herpes simplex virus have been conducted in patients with malignant glioma (a form of brain cancer) and colorectal cancer that has spread to the liver.
In gene transfer, researchers introduce a foreign gene directly into cancer cells or into surrounding tissue. The goal is that the newly inserted gene will cause the cancer cells to die or prevent cancer cells and surrounding tissue from funneling blood to tumors, depriving them of nutrients they need for survival. While this approach has a great deal of promise, it presents scientists with several obstacles as well, including “gene silencing,” in which the implanted genes fail to switch on. In animal studies, gene transfer techniques achieved positive results in treating prostate, lung, and pancreatic tumors.
Various approaches to gene transfer have been tested in clinical trials. These trials have involved cancers including squamous cell cancer of the head and neck, liver, ovaries, prostate, bladder, and other organs.
CAR T-cell therapy, which seeks to enhance the natural cancer-fighting ability of patients’ own T cells, is one type of immunotherapy. A sample of a patient’s T cells is collected and mixed with viruses carrying several specific genes. The viruses deliver these genes to the T cells’ nuclei, where they’re incorporated into the cells’ DNA. The genes cause the T cells to express a special protein called a chimeric antigen receptor, or CAR, on their surface. The CAR directs the T cell to the tumor cell using a specific “address,” and the CAR T cell is then equipped to rapidly destroy the cancer cell. When the cells, now called CAR T cells, are infused into the patient, they seek out tumor cells and then proliferate to generate many more cancer-killing cells.
In clinical trials, CAR T-cell therapy has achieved dramatic results in some children and adults with leukemia or lymphoma. However, the success of this approach is associated with severe side effects in some individuals. Last year, the U.S. Food and Drug Administration approved one CAR T-cell therapy as standard treatment for children with ALL and a second for adults with advanced lymphomas. Trials for patients with certain types of solid tumors are beginning to open.
Another form of immunotherapy involving gene therapy is cancer vaccines. This approach involves collecting tumor cells from a patient and engineering them with genes that cause them to be more conspicuous to the immune system. The altered cells are then re-infused into the patient along with an immune-stimulating compound. The patient’s immune system launches a vigorous attack not only on the newly-infused cancer cells but also on similar cells throughout the body.