One injection resets the immune system, showing promise for intractable autoimmune diseases with in vivo CAR-T

An “in vivo CAR-T” therapy that resets the immune system of patients with intractable autoimmune diseases with a single injection showed efficacy in an early clinical study.

According to BioOn on the 20th (local time), when U.S. researchers administered a single intravenous injection of a novel therapy called “JY231” to 16 patients with neurologic and neuromuscular autoimmune diseases who had not responded to standard treatment, all patients showed improvements in symptoms and biological markers. The findings were published in the medical journal New England Journal of Medicine (NEJM).

Existing CAR-T cell therapy involves collecting a patient’s T cells, genetically modifying them in the laboratory and reinfusing them. The process is costly and time-consuming and also requires preconditioning chemotherapy.

By contrast, JY231 carries genetic instructions in a harmless virus, a lentiviral vector, to reprogram T cells directly inside the body. The infused cells reached peak levels in 11 days and spread throughout the body.

The study included seven patients with progressive multiple sclerosis (MS), three with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), three with generalized myasthenia gravis (gMG) and three with idiopathic inflammatory myopathy (IIM).

The treatment rapidly eliminated B cells that drive autoimmune attacks by targeting them. Although B cells recovered after about 2 months, most were newly generated cells and were completely different from those present before treatment. The researchers assessed this as essentially resetting the immune system.

The treatment was highly precise, with more than 99% of the reprogrammed cells converted into the intended disease-fighting cells.

After 6 months, the seven patients with MS had reduced physical disability, improved cognitive function and substantially less fatigue. Patients with gMG and MOGAD had markedly reduced levels of autoantibodies that attack the nervous system, while those with IIM had improved muscle strength.

No neurologic adverse effects occurred. However, about 69% of patients experienced a mild immune reaction called cytokine release syndrome, which resolved in all patients within 2 weeks.

The researchers described the findings as an early proof of concept for treating intractable neurologic autoimmune diseases, while noting that larger randomized clinical trials are needed to confirm long-term safety and efficacy.