Cell and gene therapies are medicines that address the underlying causes of diseases at the genetic and cellular level. Unlike traditional pharmaceuticals that manage symptoms or surgeries that remove diseased tissue, these advanced treatments aim to modify a person’s biological makeup. They offer long-lasting therapeutic effects, providing new possibilities for conditions previously considered untreatable.
Distinguishing Between Cell and Gene Therapy
Gene therapy involves modifying a person’s genes to treat disease by correcting genetic faults or introducing new genetic material. It uses two primary approaches. In in vivo gene therapy, genetic material is delivered directly into the patient’s body, often using modified viruses as vectors to carry genes to target cells (e.g., in the eye or brain). Conversely, ex vivo gene therapy involves removing cells from the patient, modifying them genetically in a laboratory, and then reintroducing them into the body. It is often used for blood disorders where cells are easily accessible.
Cell therapy introduces new, healthy cells into a patient’s body to replace diseased or damaged ones, or to provide a therapeutic function. These cells can be sourced from the patient themselves (autologous) or from a donor (allogeneic). Examples include stem cell transplants, which replace unhealthy blood-forming cells, or immune cell therapies, which use the body’s own defense mechanisms. It aims to restore or alter specific cell populations to treat various conditions, including cancers and degenerative diseases.
Overlap exists where treatments combine aspects of both cell and gene therapy. Many advanced therapies are considered both because they involve genetically modifying cells before introducing them into the body. A key example is Chimeric Antigen Receptor (CAR)-T cell therapy, used for certain blood cancers. In CAR-T therapy, a patient’s own T-cells are collected and then genetically engineered in a lab to express a special receptor (CAR) to recognize and attack cancer cells. These modified cells are then expanded and infused back into the patient, making it a cell therapy (due to cell transfer) and a gene therapy (due to genetic modification).
Conditions Treated by Cell and Gene Therapies
Cell and gene therapies are being developed and approved for a growing range of conditions, particularly those with a clear genetic basis or where cellular dysfunction is involved. For inherited genetic disorders, these therapies offer a way to address the root cause by correcting or replacing a faulty gene. For instance, onasemnogene abeparvovec (Zolgensma) treats spinal muscular atrophy (SMA), a muscle-wasting condition, by delivering a functional copy of the SMN1 gene. Similarly, voretigene neparvovec (Luxturna) targets inherited forms of vision loss, such as Leber congenital amaurosis, by providing a healthy gene to retinal cells. Exagamglogene autotemcel (Casgevy) is approved for sickle cell disease and beta thalassemia, both genetic blood disorders.
In the field of cancer, cell therapies, particularly CAR-T cell therapies, have shown success in treating specific blood cancers. These include certain types of leukemia and lymphoma, where genetically engineered immune cells are used to target and destroy cancer cells. Approved CAR-T therapies like tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta) have improved treatment for patients with relapsed or refractory B-cell acute lymphoblastic leukemia and large B-cell lymphoma, respectively.
Beyond these established applications, research continues into emerging areas. Scientists are investigating the potential of cell and gene therapies for autoimmune diseases, where the immune system mistakenly attacks the body’s own tissues. Degenerative conditions, such as Parkinson’s disease, and infectious diseases like HIV, are also areas of active exploration for these advanced therapeutic approaches.
The Patient’s Journey
The process for receiving an ex vivo cell and gene therapy, such as CAR-T cell therapy, involves several stages over a period of weeks. It begins with cell collection, often through a procedure called apheresis. During apheresis, blood is drawn from the patient, and a specialized machine separates and collects specific cells, such as T-cells, while returning the remaining blood components to the patient’s body. This collection usually takes several hours to gather enough cells for modification.
Following collection, the isolated cells are transported to a specialized manufacturing facility. Here, the cells undergo a genetic engineering process, introducing new genetic material to reprogram them for their therapeutic function. For CAR-T therapy, this means inserting a gene that enables the T-cells to produce chimeric antigen receptors, allowing them to recognize cancer cells. This manufacturing and expansion phase can take several weeks, during which the patient may receive other treatments to manage their disease.
While the cells are being prepared, the patient may undergo a preparatory regimen, most commonly lymphodepleting chemotherapy. This chemotherapy aims to reduce the number of existing lymphocytes in the patient’s body, creating “space” for the newly engineered cells to expand and function effectively upon re-infusion. The specific chemotherapy regimen and its intensity depend on the type of therapy and the patient’s condition.
The final step is the infusion of the modified cells back into the patient, a process similar to a standard blood transfusion. The prepared cell product is delivered intravenously, typically over a short period. After infusion, patients are closely monitored in a specialized center for several weeks. This monitoring period is important to detect and manage potential side effects, such as cytokine release syndrome or neurological events, and to assess the initial response to the therapy.
Approval and Access to Treatment
Regulatory bodies, such as the U.S. Food and Drug Administration (FDA), oversee the development and approval of cell and gene therapies. These agencies evaluate the safety and efficacy of these complex treatments through clinical trials before they can be made available to patients. Since 2017, the FDA has approved a growing number of cell and gene therapies for various conditions, including Kymriah for certain blood cancers and Zolgensma for spinal muscular atrophy.
Despite their therapeutic promise, cell and gene therapies face challenges regarding widespread accessibility. One barrier is their high cost, with prices often ranging from hundreds of thousands to several million dollars per dose. For example, Hemgenix, a gene therapy for hemophilia B, is priced at approximately $3.5 million per dose, while Zolgensma costs around $2.1 million. These high costs raise concerns about the financial strain on healthcare systems and individual patients.
The personalized nature of the manufacturing process also limits accessibility. Many of these therapies, particularly autologous ones like CAR-T, involve collecting cells from individual patients, modifying them in a specialized facility, and then returning them to the same patient. This manufacturing process is resource-intensive, time-consuming, and difficult to scale, contributing to both the high cost and logistical hurdles in making these treatments widely available. Addressing these challenges requires collaborative efforts across industry, regulatory bodies, and healthcare providers to develop more efficient manufacturing methods and sustainable reimbursement strategies.