Body-Designed Immunotherapy May Alleviate Multiple Sclerosis Symptoms

Symptoms improved in 16 people with multiple sclerosis and other autoimmune diseases after they received an experimental treatment that prompts the body to produce disease-fighting immune cells, researchers report.¹ The findings come from a small early-stage clinical trial, and researchers caution that the treatment must be tested in larger studies before its safety and effectiveness can be established.

The researchers used a modified virus to deliver genetic instructions directly into participants’ immune cells, known as T cells. These instructions enabled the cells to produce chimeric antigen receptors (CARs). The resulting CAR T cells were designed to target B cells, which produce the autoantibodies that attack healthy tissues in people with autoimmune disease.

“This is a very exciting proof-of-concept study,” says David Simon, a clinician and researcher at the Faculty of Medicine of the Charité University of Berlin. The approach, known as in vivo CAR-T cell therapy, could be faster and less expensive to manufacture than conventional CAR-T treatments, which are produced outside the body, he adds.

Traditional CAR T-cell therapy involves removing T cells from a person’s blood and genetically modifying them in a laboratory to produce CARs. The engineered cells are then expanded and infused back into the patient. In vivo CAR-T therapy aims to carry out this genetic reprogramming inside the body instead. CAR-T cell therapies are already used to treat some blood cancers, and clinical trials are investigating their potential against autoimmune conditions such as lupus.

“Developing in vivo CAR-T cell therapy for autoimmune diseases would be a major achievement,” says Bin Du, an immunologist at East China Normal University in Shanghai. However, he says that further research is needed to determine whether the treatment can provide lasting benefits.

Dai-Shi Tian, one of the study’s principal investigators, says the results are encouraging but preliminary. “Although the response is a promising signal, there is still no conclusive evidence of efficacy or durable restoration of immune tolerance,” says Tian, a neurologist at Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China.

Immune reset

The trial included people with multiple sclerosis and other autoimmune disorders that cause muscle weakness, inflammation or attacks on the brain, spinal cord and eyes. Each participant received a single intravenous injection containing the viral vector, and researchers monitored them for approximately six months.

The research team used a lentivirus developed by the Chinese biotechnology company Shenzhen Genocury Biotech. Lentiviral CAR-T cell therapies have also been investigated for blood cancers, with research reporting promising treatment responses.²

After treatment, participants produced increasing numbers of CAR T cells. These cells reduced the number of B cells and lowered levels of autoantibodies that target healthy tissues. The replacement B cells did not appear to produce the same harmful autoantibodies, suggesting that the therapy might temporarily reset part of the immune system.

Participants with multiple sclerosis experienced improvements in motor and cognitive function, along with reduced fatigue. People with autoimmune diseases affecting the muscles showed stronger muscle function and lower levels of inflammation. Researchers say longer follow-up and larger, controlled clinical trials will be necessary to determine how durable these improvements are and whether in vivo CAR-T therapy can safely restore immune tolerance.