By Mary Bolster
How does CAR T-cell therapy work?
Chimeric antigen receptor (CAR) T-cell therapy is an immunotherapy, originally developed to treat certain types of cancers and now being trialed as a therapy for autoimmune diseases.
T-cells are immune cells that occur naturally in the body. Their job is to fight off infectious agents like bacteria, viruses, and even tumors.
In CAR T-cell therapy, doctors harvest a patient’s T-cells and modify them with a chimeric antigen receptor – using either DNA or RNA – then return them to the patient’s body, where they destroy immune cells like b-cells.
The targeting mechanism in cells modified by DNA is more permanent, says Dr. Ulane, who is involved in two CAR T-cell trials currently underway. When those cells are put back in the body, they will expand and grow. Cells modified by RNA are not permanent and will not expand indefinitely.
“This means, practically speaking, that the effects of DNA therapy are typically more robust and long-lasting and may be considered a onetime immune system reset,” she says. “While the effect of RNA therapy may be equally robust, it can wear off.” That’s why a patient like Danny DeBerry, who has been in an mRNA CAR-T trial for four years, must be reinfused every 18 months or so.
CAR T-cell therapy is tantalizingly adaptable, says Dr. Ulane. The T-cell can be modified to target highly specific cells in the body, as well as being personalized to each patient by using a patient’s own cells.
Adaptations of CAR T-cell therapy
As scientists continue to understand and refine CAR T-cell therapy, they are finding new ways to apply and tweak it. One is targeting a specific antibody in myasthenia gravis. Called chimeric autoantibody receptor, it targets b- cells that have a specific type of antibody. Regular CAR T-cell therapy targets all b-cells.
“You’re not wiping out all the immune b-cells,” says Dr. Ulane. “This is a further development that is more specific to one type of MG, in this case the MuSK antibody.”
Other target cells being studied are CD19, a molecule on the surface of B cells and cancerous B cells, and B cell maturation antigen (BCMA), a protein found at high levels in people with multiple myeloma.
Is CAR-T-cell therapy a “holy grail”?
The ongoing research in CAR T-cell therapy for autoimmune disease – there are more than 130 industry-sponsored trials in progress – is exciting, experts say.
“It’s the frontier for myasthenia gravis,” says Miriam Fremier, MD, clinical professor of neurology at The Ohio State University Wexner Medical Center. “It has the potential to be pretty amazing, but we don’t have all the details yet.”
Dr. Aimee Payne, MD, an MGFA grant recipient who is investigating a novel autoantibody receptor T-cell therapy, agrees. She and others cite a trial in Germany in 2021 in which a young woman with lupus went into complete remission and has been off treatment and free of symptoms for four years.
“This could be the holy grail,” says Dr. Payne, “a one-and-done treatment that can induce long-term remission.”
This article was developed based on primary research, including interviews and publicly available research on MG.