A revolutionary cancer treatment could transform autoimmune disease

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 risk between the impacts of an autoimmune disease, which can vary widely in severity, and the difficult-to-quantify risk of side effects or future cancers remains a major open question.

Researchers are already working on second- and third-generation versions of CAR T cells that they hope will be safer against cancer and autoimmunity. For example, James Howard, a neuromuscular neurologist at the University of North Carolina at Chapel Hill, is testing technology from a company called Cartesian Therapeutics that encodes CAR using mRNA molecules, the short-lived genetic messenger used in Covid-19 vaccines, instead of long-lived DNA. CAR T cells should eliminate B cells as long as the mRNA persists, then lose their B cell targeting abilities. With no chance for the genetically modified T cells to persist long term, there should be no risk of cancer.

Another advantage of the Cartesian approach: Doctors infuse these T cells in sufficient numbers that they don’t need to reproduce in the patient’s body, which Howard says 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.

Dealing with CAR T sticker shock

Beyond side effects, the other major challenge facing CAR T therapy is its price tag, which runs into the 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 remove the step of engineering and growing the cells in the lab. Lunning says he envisions future procedures that would modify a person’s T cells in their own body instead of doing the genetic engineering in the lab.