Credit: Govind Bhagavatheeshwaran, Daniel Reich, National Institute of Neurological Disorders and Stroke, National Institutes of Health
A small-scale clinical trial has demonstrated that in vivo CAR-T-cell therapy can effectively alleviate symptoms of multiple sclerosis and other autoimmune disorders by reprogramming the immune system from within. Using a modified virus to deliver genetic instructions directly into the bloodstream, researchers successfully prompted the body to produce specialised cells that eliminate disease-causing B cells.
This in vivo approach promises to be cheaper and faster than current CAR-T-cell therapies. While participants showed significant functional improvements and manageable side effects, the researchers stress the need for long-term monitoring to assess potential risks like tumour development.
This trial, published in The New England Journal of Medicine, used a modified virus to transfer genetic instructions for making chimaeric antigen receptors (CARs) on T cells. The CAR T cells target autoantibodies expressed by B cells, which in autoimmune diseases, attack the body’s own healthy tissue.
“This is a very exciting proof-of-concept study” for in vivo CAR-T-cell therapy, which is made inside the body, says David Simon, a clinician-researcher at the Charité –University Medicine Berlin. In vivo therapy is cheaper and faster to produce than is conventional CAR-T-cell therapies that are made in a laboratory, he adds.
The trial involved people with multiple sclerosis and other autoimmune conditions. The participants received a single injection of the viral cells into their bloodstream and were monitored for about six months.
The team used a virus called a lentivirus, which last year was used for another CAR-T-cell therapy which was shown to effectively treat blood cancer.
The team reported that, following treatment, the participants generated more CAR T cells over time. These helped to deplete the number of B cells and levels of autoantibodies that attack healthy tissue.
The team says the participants’ replacement B cells did not produce such autoantibodies, suggesting that their immune systems had been reset. The people with multiple sclerosis showed improved motor and cognitive function, as well as reductions in fatigue.
Those with other conditions affecting their muscles showed improved scores for muscle strength and decreased inflammation. Simon says the efficacy seems promising and the risk of side effects was manageable.
A mild inflammatory response was experienced by participants, but lasted no longer than two weeks, and three participants had mild to moderately low levels of white blood cells, which later recovered to a typical level. However, it will be necessary to follow participants for ten years to properly assess the risk of long-term side effects.
If these promising results are validated in larger studies, this technique could represent a revolutionary shift in treating chronic autoimmune conditions.
Source: Nature
