E25: Tuning the CAR T
Patients’ cells can be retooled, but caution is required
T-cells are one of the human body’s most powerful immune cells. By “souping up” those cells in a lab, researchers can develop immunotherapies for cancers like leukemia and lymphoma – the first two cancers to have FDA-approved CAR T therapies.
“T cells are the cells in your immune system that play an important role in eliminating foreign invaders,” said Sanne Holt, Group Leader in Biology for Charles River’s Leiden site and our podcast guest. "Chimeric antigen receptors (CAR) can be designed in the lab to bind to only one specific target. If you add this engineered CAR onto a T cell, you generate a new T cell which has the ability to bind and kill specific cells which express that target that you designed your CAR for.”
CAR T therapies are promising but come with warnings. One serious risk for patients is cytokine release syndrome – when a large number of cytokines (signaling proteins) are released into the body in response to the modified T cells, leading to acute inflammation and organ failure. This condition has been in the news recently as a possible contributing factor to severe cases of COVID-19.
“When your immune system gets activated due to a virus or bacterial infection, your immune cells (mainly your T cells and monocytes) start producing a variety of cytokines to trigger killing of the invader," Sanne said in a follow-up conversation. “With a cytokine storm, this response is so strong that the immune cells ‘get out of hand’ and start causing damage to healthy cells. Your own immune system, the thing that is supposed to protect you, then actually starts attacking your organs causing lung damage and organ failure.”
Luckily, according to Sanne, there are already drugs on the market to treat cytokine release syndrome caused by CAR T therapies. To learn more about CAR T, listen to this episode of Sounds of Science.