Leukapheresis is a medical procedure where a machine separates and collects white blood cells from a person’s blood. This process is the first step for CAR T-cell therapy, a form of immunotherapy that modifies a patient’s own T-cells to better recognize and fight cancer. Leukapheresis provides the T-cells that will be engineered to become the treatment itself, preceding the complex laboratory and clinical steps of the therapy.
The T-Cell Collection Process
The journey into CAR T-cell therapy begins with a preparatory step to ensure the collection process is effective. For many patients, this involves the placement of a central venous catheter, a thin, flexible tube inserted into a large vein in the chest or neck. This catheter provides stable vascular access for the hours-long procedure and avoids issues with peripheral veins, which might not withstand the continuous draw and return of blood.
With access established, the patient is connected to an apheresis machine. This machine draws blood from the body and sends it through a centrifuge, which spins at high speed to separate the components by density. This process isolates the mononuclear cells, a category of white blood cells that includes the T-cells needed for the therapy.
While the machine collects the targeted T-cells, the remaining blood components—red blood cells, platelets, and plasma—are returned to the patient’s body. The procedure lasts between three to four hours, during which the patient is awake and can engage in quiet activities like reading or watching movies. Some individuals may experience temporary side effects, like a tingling sensation or feeling cold, related to the anticoagulant used to prevent clotting.
The primary goal is to collect a sufficient quantity and quality of T-cells to manufacture the CAR T-cell product. The collected cells are bagged and prepared for transport to a specialized manufacturing facility. This step marks the end of the patient’s direct involvement for several weeks, as the focus shifts to the engineering process.
Engineering the T-Cells in the Laboratory
Once the patient’s T-cells arrive at the manufacturing facility, they begin a transformation into a targeted cancer therapy. The initial step involves isolating and activating the T-cells from the collected leukapheresis product. This activation prepares the cells to receive new genetic instructions, a process for creating CAR T-cells.
The engineering process is the genetic modification of these activated T-cells. Scientists use a disarmed virus as a delivery vehicle, or vector, to carry a synthetic gene into the T-cells. This gene holds the instructions for building a Chimeric Antigen Receptor (CAR), and it integrates into the cells’ own DNA, instructing them to produce these new receptors on their surface.
After the T-cells are modified, they are not yet ready for infusion. The next stage is expansion, where the engineered CAR T-cells are grown in a bioreactor until they number in the millions or even billions. This multiplication is necessary to ensure there is a large enough army of cells to effectively combat the cancer, and the entire process can take several weeks.
Preparing for and Receiving the CAR T-Cell Infusion
While the CAR T-cells are being manufactured, the patient’s clinical team prepares their body to receive the engineered cells. A few days before the infusion, the patient undergoes a short course of lymphodepleting chemotherapy. This chemotherapy reduces the number of existing lymphocytes, including T-cells, circulating in the body.
This reduction of the patient’s native immune cells creates a more favorable environment for the incoming CAR T-cells. By clearing out existing lymphocytes, the lymphodepletion makes physical space and reduces competition for resources. This allows the new CAR T-cells to expand more effectively and persist longer after infusion. The chemotherapy agents used for this purpose are often fludarabine and cyclophosphamide.
Once lymphodepletion is complete and the manufactured CAR T-cells have arrived back at the treatment center, the infusion can take place. The frozen cells are thawed and prepared. The infusion process itself is often straightforward and quick, sometimes taking less than 30 minutes, and is administered through the patient’s central line much like a blood transfusion.
Post-Infusion Monitoring and Management
The period following the infusion of CAR T-cells is a time of intense monitoring, as the engineered cells multiply and attack the cancer. This immune activation is what makes the therapy effective, but it can also trigger significant side effects. Patients are monitored closely, often within a hospital setting, for the first few weeks to manage these potential toxicities and allow for prompt intervention.
One of the most common and serious side effects is Cytokine Release Syndrome (CRS). This condition occurs when activated CAR T-cells release a massive flood of inflammatory molecules called cytokines, leading to a systemic inflammatory response. Symptoms often resemble a severe flu but can escalate to life-threatening issues like low blood pressure and difficulty breathing, though effective treatments are available.
Another potential complication is Immune Effector Cell-Associated Neurotoxicity Syndrome, or ICANS. This syndrome affects the nervous system and can manifest in various ways, including confusion, difficulty with language, headaches, or in severe cases, seizures. The symptoms of ICANS can occur alongside CRS or appear days after it has resolved, and it is manageable with specific treatments.
The highest risk for developing new-onset CRS and ICANS is within the first two weeks after the infusion, and the incidence of these toxicities drops significantly after this period. This intensive monitoring period is a defining feature of the immediate post-infusion experience, focusing on managing the powerful effects of the therapy while it begins to work against the cancer.