Results of a small clinical trial suggest a type of immunotherapy that produces modified cells directly inside the patient’s body reduced symptoms of MS and several other autoimmune diseases. Researchers call the preliminary results encouraging but emphasize that larger studies and long-term patient follow-up are needed to prove the method’s effectiveness and safety.
In this study, published in The New England Journal of Medicine, 16 people with MS and other autoimmune diseases received a treatment in which immune cells called T cells are redesigned and engineered directly inside their bodies to fight the disease-causing cells.
Nature’s website writes that researchers used a modified virus to deliver the genetic instructions needed to make a chimeric antigen receptor to T cells. After this change, the T cells become CAR-T cells and target a group of B cells that play a role in producing autoantibodies.
In autoimmune diseases, the immune system mistakenly attacks the body’s healthy tissues. Therefore, reducing the B cells involved in this process provides an opportunity to reset immune system function.
David Simon, a clinical researcher at Charité – Universitätsmedizin Berlin who did not participate in the study, described the research as an important step in demonstrating the possibility of producing CAR-T cells inside the body. He said that if successful, this method would be faster and cheaper than conventional ways of producing CAR-T cells.
Making therapeutic cells inside the body
In conventional CAR-T methods, a blood sample is first taken from the patient and the T cells are genetically engineered in a laboratory. These cells are expanded and returned to the patient’s body. This method is currently used to treat some blood cancers, and in recent years researchers have tested its efficacy on autoimmune diseases such as lupus.
But the new method has one important difference: T cells are not removed from the body and redesigned in the lab; instead, the genetic instructions are delivered directly to the T cells inside the body so that the body itself produces the CAR-T cells.
Bing Du, an immunologist at East China Normal University in Shanghai, considers developing a method to produce CAR-T cells inside the body an important achievement and believes its initial results are comparable to some CAR-T therapies in which cell engineering is done outside the body.
However, researchers caution against premature conclusions.
Dai-Xi Tian, a lead researcher on the study and a neurologist at Tongji Medical College of Huazhong University of Science and Technology in Wuhan, says the therapeutic responses observed in patients are encouraging, but it cannot yet be considered definitive evidence of complete efficacy or permanent resetting of the immune system.
Attempting to “reset” the immune system
Participants in this trial had MS and several other autoimmune diseases, including disorders involving muscle weakness or inflammation and diseases in which the immune system attacks the brain, spinal cord, or eyes.
Each patient received a single injection and was then monitored for about six months. Researchers used a modified lentivirus designed by the biotech company Shenzhen Genocury Biotech in China to deliver the genetic instructions. In this method the lentivirus acts as a carrier and delivers the necessary genetic material into T cells so that those cells can produce the desired receptor.
Results showed that after treatment the number of CAR-T cells in participants’ bodies gradually increased. At the same time, the number of B cells and levels of autoantibodies associated with attacks on healthy tissues decreased.
Researchers also observed that the new B cells that replaced the previous ones after treatment did not produce the same autoantibodies. This finding may indicate partial resetting of the immune system, although longer studies are needed to prove the durability of this effect.
Improvements in mobility, cognitive function, and fatigue in MS patients
People with MS showed improvements in some measures of motor and cognitive performance after treatment, and their fatigue decreased. In patients whose autoimmune disease affected muscles, muscle strength improved and signs of inflammation decreased.
According to Simon, the initial efficacy of the treatment appears promising and the side effects observed in this study were mostly manageable.
Most participants experienced a mild inflammatory reaction that did not last more than two weeks. In three people white blood cell counts fell mildly to moderately but returned to the normal range shortly thereafter.
Simon says if these results are confirmed in larger studies with longer follow-up and a control group, this technology could bring a major change in the treatment of some autoimmune diseases.
Why must patients be monitored for years?
Despite the encouraging results, one of the most important questions about this method concerns its long-term safety.
Lentiviruses insert genetic material into the patient’s cells’ DNA. For this reason there is concern that unintended changes in cells could, in the future, lead to complications such as cancer. Bing Du says people treated with this method should be monitored for at least a decade to assess the risk of late complications, including tumor formation.
He adds that proving sufficient safety for this technology before wide clinical use will still require more time and evidence. Tian also says participants in this trial will be monitored in coming years for the possibility of cancer, infection, disease relapse, and other potential late complications.
Researchers also plan to start larger studies each focused on a specific autoimmune disease. Such studies will determine whether producing CAR-T cells directly in the body will move from an experimental technique to a practical option for treating MS and other autoimmune diseases.