Matt Lunning, MD, medical director of gene and cell therapy at Nebraska Medicine in Omaha, says that causing a secondary cancer may be an acceptable risk when treating a life-threatening cancer, but not for autoimmunity. How to balance the risk between the effects of autoimmune disease, which can vary widely in severity, and the risk of future side effects or cancers, which are difficult to measure, remains a major open question.
Researchers are already working on second- and third-generation versions of CAR T, which they expect to be safer for both cancer and autoimmunity. For example, James Howard, a neuromuscular neuroscientist at the University of North Carolina at Chapel Hill, is testing technology from a company called Cartesian Therapeutics. mRNA moleculesA short-lived genetic messenger used instead of long-lived DNA in Covid-19 vaccines. CAR T cells should only delete B cells as long as the mRNA persists, then lose the ability to target B cells. Unless genetically modified T cells have a chance to survive long-term, there should be no risk of cancer.
Another advantage of Cartesian’s approach: Doctors infuse enough of these T cells that they don’t need to multiply in the patient’s body, which Howard says reduces the risk of inflammation. In the latest trial, 15 people with autoimmune diseases received Cartesian CAR T treatment; two-thirds saw an improvement in their symptoms and none suffered long-term serious side effects.
Treatment of CAR T sticker shock
Aside from side effects, another major challenge facing CAR T therapy is the price tag, which can reach hundreds of thousands of dollars, including hospital stays, cell engineering, and other costs.
Treatment would be cheaper and simpler if scientists eliminated the need for individualized engineering of each patient’s own cells and instead used donor cells, or could cut out the step of engineering and growing cells in the lab. Lunning says he is considering future procedures that would modify a person’s T cells in their own bodies instead of doing genetic engineering in a lab.
