Gene therapy for cancer is a transformative approach, moving beyond conventional treatments like chemotherapy and radiation. This innovative strategy uses genetic material as medicine to combat disease at its root within cells. Unlike broad-targeting therapies, gene therapy precisely modifies or introduces genes to address the genetic alterations driving cancer growth. This highly targeted method aims to reprogram cells to fight the disease.
How Gene Therapy Fights Cancer
Gene therapy fights cancer using several biological strategies. Gene replacement substitutes a mutated or missing gene with a healthy copy. For example, a non-functional tumor suppressor gene like p53 can be replaced with a working version to restore cell growth control.
Gene inactivation “turns off” or silences genes improperly promoting cancer growth, such as overactive oncogenes that cause uncontrolled cell proliferation. Deactivating these genes halts abnormal signals driving tumor expansion.
Gene therapy also introduces new genes into cancer or immune cells to enhance the body’s defenses. These genes can make cancer cells more visible to the immune system, directly trigger their death, or prevent tumors from developing a blood supply, starving them of nutrients.
Types of Gene Therapy Approaches
Gene therapy utilizes various methods to deliver genetic material, each designed for specific therapeutic goals. One prominent example is Chimeric Antigen Receptor (CAR) T-cell therapy, which involves extracting a patient’s own T-cells through leukapheresis. These collected T-cells are then genetically engineered in a laboratory to express a Chimeric Antigen Receptor (CAR) on their surface. This CAR is a synthetic protein that allows the T-cells to specifically recognize and bind to unique proteins, or antigens, found on the surface of cancer cells. Once engineered and multiplied, these “living drugs” are infused back into the patient, where they actively seek out and destroy cancer cells throughout the body.
Oncolytic virus therapy employs viruses that are naturally or genetically modified to selectively infect and destroy cancer cells while leaving healthy cells unharmed. An example is Talimogene Laherparepvec (T-VEC), a modified herpes simplex virus, injected directly into melanoma tumors. The virus replicates within the cancer cells, causing them to burst and die. It also releases tumor antigens and stimulating factors that activate the patient’s immune system to mount a broader anti-cancer response.
Therapeutic cancer vaccines represent another approach, working by introducing genetic material, often messenger RNA (mRNA), that instructs the body’s cells to produce specific cancer-related proteins or antigens. These antigens then train the patient’s immune system, particularly T-cells, to recognize and attack cancer cells that express these same proteins. Unlike traditional vaccines that prevent disease, therapeutic cancer vaccines are designed to treat existing cancer by stimulating an active immune response against it.
Cancers Treated With Gene Therapy
Gene therapy has shown considerable success in treating specific types of cancer, with a growing number of therapies receiving regulatory approval. CAR T-cell therapies are currently approved for several blood cancers, including certain forms of B-cell acute lymphoblastic leukemia (ALL) in pediatric and young adult patients, as well as various types of non-Hodgkin lymphoma and multiple myeloma in adults. These therapies target specific markers, such as CD19 or BCMA, found on the surface of these cancer cells.
Oncolytic virus therapy, exemplified by T-VEC, is approved for the treatment of melanoma that has spread to the skin or lymph nodes. This treatment is administered by direct injection into the tumor lesions. Ongoing clinical trials are exploring gene therapy’s application in a broader range of solid tumors and other blood cancers, with researchers investigating new targets and delivery methods.
The Patient Treatment Journey
Undergoing gene therapy, particularly CAR T-cell therapy, involves a structured and closely monitored process. The journey begins with a thorough consultation and evaluation, where a multidisciplinary team assesses the patient’s overall health, cancer type, and previous treatments to determine suitability. This assessment often includes various tests and scans.
If deemed eligible, the next step is cell collection through leukapheresis. During this procedure, blood is drawn from the patient, and a specialized machine separates and collects the T-cells, returning the remaining blood components. This process usually takes several hours over one or two days.
The collected T-cells are then sent to a specialized manufacturing facility, where they undergo genetic engineering to become CAR T-cells. This process can take a few weeks. While the cells are being modified, the patient may receive “bridging therapy” to manage their cancer until the engineered cells are ready. Before the infusion of CAR T-cells, patients typically undergo a short course of “conditioning chemotherapy.” This mild chemotherapy helps reduce existing immune cells, creating a more favorable environment for the newly introduced CAR T-cells to expand and function effectively.
Once the engineered cells are ready, they are infused back into the patient, similar to a blood transfusion, which usually takes less than an hour. Following the infusion, patients enter a crucial monitoring and recovery period, often requiring hospitalization for several weeks. During this time, the medical team closely observes for potential side effects and assesses the treatment’s response, providing supportive care as needed.
Safety and Regulatory Considerations
Gene therapy, while promising, can have specific side effects managed by medical teams. Two common potential side effects, particularly with CAR T-cell therapy, are Cytokine Release Syndrome (CRS) and neurotoxicity. CRS occurs when activated CAR T-cells release inflammatory proteins (cytokines) into the bloodstream. Symptoms range from flu-like manifestations (fever, chills, fatigue, muscle pain) to severe issues like low blood pressure, difficulty breathing, and organ dysfunction. Medical teams monitor for CRS and treat it with medications like tocilizumab, which blocks cytokine effects.
Neurotoxicity, also referred to as Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), affects the central nervous system. Its symptoms can include confusion, difficulty speaking, headaches, tremors, or seizures. While the exact mechanisms are still being studied, it often correlates with the severity of CRS and typically occurs within days to weeks after infusion. These neurological effects are also closely monitored and managed by the healthcare team, often with corticosteroids.
The development and approval of gene therapies are subject to rigorous oversight by regulatory bodies like the U.S. Food and Drug Administration (FDA). The FDA evaluates these complex biological products through stringent processes, including extensive preclinical testing and multiple phases of clinical trials, to ensure their safety and effectiveness. This regulatory framework involves assessing manufacturing procedures, the safety of gene delivery vectors, and the long-term persistence and expression of the introduced genes. The FDA also employs expedited pathways, such as Breakthrough Therapy designation, to accelerate the development and review of therapies, ensuring innovative treatments reach patients while maintaining high safety standards.