New research challenges conventional treatments for autoimmune disease

Scientists are exploring a groundbreaking strategy to treat rheumatoid arthritis, multiple sclerosis, lupus, and other serious autoimmune disorders — by reprogramming patients’ malfunctioning immune systems rather than merely suppressing them.

Researchers are working to reshape dysfunctional immune responses in ways that could be both more powerful and more precise than existing therapies, according to reporting by AP.

Currently, when the immune system mistakenly turns against the body, treatments aim to dampen the attack but don’t correct the underlying problem. Patients often depend on lifelong medications — pills, injections, or infusions — that are expensive, can cause significant side effects, and frequently fail to fully control the disease.

“We’re entering a new era,” said Dr. Maximilian Konig, a rheumatologist at Johns Hopkins University researching several of these emerging treatments. They represent “the chance to control disease in a way we’ve never seen before.”

These treatments are still highly experimental and, due to potential risks, are mostly limited to patients who have run out of standard options. Still, people joining early trials are hopeful.

CAR-T therapy — originally developed to engineer a patient’s own T cells to attack cancer — is gaining attention for autoimmune disease. In blood cancers like leukemia and lymphoma, the cancerous cells are B cells, which also play a central role in many autoimmune conditions when they malfunction.

Early US studies in mice suggested CAR-T might help. Then in Germany, Dr. Georg Schett at the University of Erlangen-Nuremberg used it to treat a severely ill young woman who had not responded to lupus therapies.

Last month, Schett told the American College of Rheumatology that his team has since treated several dozen additional patients with conditions including myositis and scleroderma — with few reported relapses so far.

These promising outcomes have triggered a surge of CAR-T clinical trials in the US and beyond for a growing number of autoimmune diseases.

How it works

Doctors first extract T cells from a patient’s blood. In the lab, those cells are engineered to attack their B cell counterparts. After patients receive chemotherapy to clear out additional immune cells, millions of these “living drugs” are infused back into the body.

While current autoimmune medications target some B cells, experts note they cannot eliminate those hidden deep within the body. CAR-T therapy can wipe out both harmful B cells and healthy ones that could later become problematic. Schett believes this deep depletion effectively resets the immune system so that newly formed B cells develop normally.

CAR-T treatment is intensive, lengthy, and expensive, partly because it is custom-made for each patient. A single CAR-T cancer treatment can cost about $500,000. Companies are now testing off-the-shelf versions made in advance from healthy donors.

Another developing method relies on “peacekeeper” cells recognized in this year’s Nobel Prize — regulatory T cells. These rare cells reduce inflammation and restrain immune cells that mistakenly attack healthy tissue. Biotech companies are engineering versions of these cells for patients with rheumatoid arthritis and other autoimmune diseases, not to attack like CAR-T, but to calm excessive immune reactions.

Scientists are also adapting another cancer therapy known as T cell engagers, which don’t require individualized cell engineering. These lab-made antibodies act like matchmakers, directing a patient’s existing T cells toward misbehaving antibody-producing B cells, explained Erlangen’s Dr. Ricardo Grieshaber-Bouyer.

Last month, Grieshaber-Bouyer reported that 10 patients with different autoimmune conditions received a course of one such drug, teclistamab. All but one saw major improvement, and six entered drug-free remission.

Guiding star for future research

Rather than broadly eliminating immune cells, Konig’s research aims to take a more targeted approach, focusing on “only that very small population of rogue cells that really causes the damage.”

B cells carry biological markers indicating their potential to produce harmful antibodies, Konig said. His team is working to engineer T cell engagers that would single out only these “bad” B cells while preserving healthy ones needed to fight infections.

In another Johns Hopkins lab, biomedical engineer Jordan Green is developing a strategy that uses messenger RNA (mRNA) — the same genetic platform used in COVID-19 vaccines — to help the immune system reprogram itself.

Green’s team uses biodegradable nanoparticles to deliver mRNA instructions that prompt key immune “generals” to suppress harmful T cells and deploy more protective ones. Once the correct immune cells absorb the instructions, the hope is they will “divide, divide, divide and make a whole army of healthy cells that then help treat the disease,” Green said.

By Nazrin Sadigova