CAR T therapy for multiple sclerosis enters US trials for first time
The first US trials of engineered cells to treat multiple sclerosis have started recruiting volunteers, raising hopes for a new therapeutic option for this devastating neurodegenerative disease and other autoimmune disorders.
CAR T cells are made by harvesting immune cells called T cells from people with diseases. The cells are then edited in a lab to produce proteins called chimeric antigen receptors (CARs), enabling them to take on a target of choice. When CAR T cells are re-infused into the person they came from, they seek out and destroy their target.
Researchers have therefore turned to CAR T cells, and specifically to those that kill B cells carrying a protein called CD19. CAR T cells are better cell killers than are the antibodies, and seem to penetrate into tissues including the brain that antibodies can’t reach. More thorough depletion of these B cells, the theory goes, should reset the malfunctioning immune system — halting the brain damage that defines the disease.
Immune reset
Neurologists have rebooted the immune system before, with promising results. In autologous haematopoietic stem-cell transplantation therapy, people with MS receive high-dose chemotherapy to kill off all their immune cells, followed by an infusion of their own stem cells to repopulate their immune system. But the risks and complexity of this therapy make it unattractive to biopharma companies, says BMS’s head of research, Robert Plenge, and it is not widely available.
CAR T cells could offer “a simpler way to reset the immune system”, says Plenge.
These cells might not be up to the task, says Mark Freedman, a neurologist at the University of Ottawa and a pioneer of the stem-cell transplantation therapy. Whereas chemotherapy can kill off all of a person’s T and B cells, CAR T cells wipe out only a subset of the B cells that contribute to the disease, he points out. But if the treatment is safe, he adds, it’s worth a try: “So much depends on safety.”
His biggest concern is brain toxicity, which can cause confusion, seizures and death and has been seen when CAR T cells have been used to treat cancer. The brains of people with MS are already inflamed, potentially exacerbating the danger, says Freedman, who consults for BMS but is not involved in the new trial.
Jeffrey Dunn, who is running the first trial of Kyverna’s CAR T cells in the United States, will be watching closely for brain toxicity, which he says seems to be linked to the number of B cells in circulation. B cells are everywhere in B cell cancers, but less abundant in MS. “We’re hoping that we see little toxicity,” says Dunn, a neurologist at Stanford University in California.
https://www.nature.com/articles/d41586-024-00470-5
The first US trials of engineered cells to treat multiple sclerosis have started recruiting volunteers, raising hopes for a new therapeutic option for this devastating neurodegenerative disease and other autoimmune disorders.
CAR T cells are made by harvesting immune cells called T cells from people with diseases. The cells are then edited in a lab to produce proteins called chimeric antigen receptors (CARs), enabling them to take on a target of choice. When CAR T cells are re-infused into the person they came from, they seek out and destroy their target.
Researchers have therefore turned to CAR T cells, and specifically to those that kill B cells carrying a protein called CD19. CAR T cells are better cell killers than are the antibodies, and seem to penetrate into tissues including the brain that antibodies can’t reach. More thorough depletion of these B cells, the theory goes, should reset the malfunctioning immune system — halting the brain damage that defines the disease.
Immune reset
Neurologists have rebooted the immune system before, with promising results. In autologous haematopoietic stem-cell transplantation therapy, people with MS receive high-dose chemotherapy to kill off all their immune cells, followed by an infusion of their own stem cells to repopulate their immune system. But the risks and complexity of this therapy make it unattractive to biopharma companies, says BMS’s head of research, Robert Plenge, and it is not widely available.
CAR T cells could offer “a simpler way to reset the immune system”, says Plenge.
These cells might not be up to the task, says Mark Freedman, a neurologist at the University of Ottawa and a pioneer of the stem-cell transplantation therapy. Whereas chemotherapy can kill off all of a person’s T and B cells, CAR T cells wipe out only a subset of the B cells that contribute to the disease, he points out. But if the treatment is safe, he adds, it’s worth a try: “So much depends on safety.”
His biggest concern is brain toxicity, which can cause confusion, seizures and death and has been seen when CAR T cells have been used to treat cancer. The brains of people with MS are already inflamed, potentially exacerbating the danger, says Freedman, who consults for BMS but is not involved in the new trial.
Jeffrey Dunn, who is running the first trial of Kyverna’s CAR T cells in the United States, will be watching closely for brain toxicity, which he says seems to be linked to the number of B cells in circulation. B cells are everywhere in B cell cancers, but less abundant in MS. “We’re hoping that we see little toxicity,” says Dunn, a neurologist at Stanford University in California.
https://www.nature.com/articles/d41586-024-00470-5