CAR T-cell therapy has revolutionized treatment of hematological malignancies, driving the enormous growth in CAR T-cell research. But while results are highly encouraging, the treatment involves multiple complex steps – from collecting and modifying the patient’s own T-cells to managing potential side effects after infusion.
Multi-step treatment process
CAR T-cell therapy starts and ends with the patient. Treatment follows a structured, multi-step process designed to maximize safety and effectiveness. Once the modified T-cells have been infused back into the patient, they mount a targeted attack to eliminate the cancer cells. Importantly, after infusion, there is a recovery phase of several weeks during which possible side effects are monitored and treated if complications occur.
Signs that the CAR T-cells are working
The time it takes for CAR T-cells to take effect can vary considerably. As a rule, the CAR T-cells begin to take effect within a few days to a few weeks after the infusion. The first signs of a reaction may be cytokine release syndrome (CRS), which usually occurs within a few days after the infusion and is an indicator that the CAR T-cells are becoming active. In some cases, the results of therapy, such as the reduction of cancer cells or complete remission, may only manifest after several months.
Potential side effects of CAR T-cell therapy
The most common side effects include CRS and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS occurs as a result of systemic inflammation triggered by rapid CAR T-cell activation and cytokine secretion. While CRS is seen to be an “on-target” effect of CAR T-cell therapy, symptoms can range from mild to life-threatening – including fever, severe hypotension, hypoxia, and multi-organ failure.
ICANS describes a complex set of neurological symptoms with varying degrees of severity that typically occur during the course of CAR T-cell therapy. The clinical appearance of ICANS varies greatly and ranges from mild forms to rapidly progressive, therapy-refractory fatal cerebral edema. An observation phase follows the recovery phase during which patients are monitored long-term for toxicities.
Future goals for CAR T-cell therapy
The success of CAR T-cell therapy has been impressive, with initial clinical remission rates as high as 90%. However, it is currently only used for a small number of patients because the process is complex, costly, and time-consuming. The production rates of existing methods are also far too low for widespread use.
Without automation, making personalized methods such as CAR T-cell therapy widely available to cancer patients will not be possible – regardless of how successful the method may be. The entire process of producing a CAR T-cell therapeutic must be brought together in a continuous system, starting with the selection of T-cells from the patient’s serum and the vector-induced activation of the T-cells on the patient-specific tumor through to the selection and isolation of the activated cells, for example using magnetic beads.
Don't miss the next part of our blog series that will focus on the viral vectors used in CAR T-cell therapy.
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