Causing a secondary cancer may be an acceptable risk when treating a life-threatening cancer, but probably not for autoimmunity, says Matt Lunning, medical director of gene and cell therapy at Nebraska Medicine in Omaha. How to balance the risk between the impacts of an autoimmune disease, the severity of which can vary widely, and the difficult-to-quantify risk of future side effects or cancers remains an important open question.
Researchers are already working on second- and third-generation versions of CAR T that they hope will be safer for both cancer and autoimmunity. For example, James Howard, a neuromuscular neurologist at the University of North Carolina at Chapel Hill, is testing a technology from a company called Cartesian Therapeutics that encodes the CAR using mRNA moleculesthe short-lived genetic messenger used in Covid-19 vaccines, instead of long-lived DNA. CAR T cells should kill B cells only as long as the mRNA persists, and then they will lose their ability to attack B cells. With no chance for the genetically modified T cells to remain long-term, there should be no risk of cancer.
Another advantage of the Cartesian approach: Doctors infuse these T cells in sufficient quantities so that they don’t need to reproduce in the patient’s body, which Howard believes reduces the risk of inflammation. In a recent trial, 15 people with autoimmune diseases received the Cartesian CAR T treatment; two-thirds saw their symptoms improve, and none suffered serious long-term side effects.
CAR T sticker impact treatment
Beyond side effects, the other big challenge facing CAR T therapy is its price, which runs into hundreds of thousands of dollars, including hospital stays, cell engineering and other expenses.
The treatment would likely be cheaper and simpler if scientists could eliminate the need for custom engineering of each patient’s own cells and instead use donor cells, or if they could eliminate the step of engineering and growing the cells in a lab. Lunning says he is studying promising procedures that would modify a person’s T cells. inside your own body instead of doing genetic engineering in a laboratory.
