Reprogramming the Immune System: New Frontiers in Treating Autoimmune Diseases

Scientists are moving beyond immune suppression to try to reset malfunctioning immune systems in hopes of more durable, precise treatments for rheumatoid arthritis, lupus, multiple sclerosis and other autoimmune diseases.

Current therapies blunt the immune system’s self-attack but rarely fix the underlying problem. Patients often face lifelong, costly medications, injections or infusions that can cause serious side effects and still fail to keep disease under control. Researchers say a new generation of approaches aims to reprogram — not just suppress — the immune response.

Patient stories underscore the promise

Mileydy Gonzalez, 35, of New York, had worsening lupus that attacked her lungs and kidneys. After joining an early study of CAR-T therapy adapted from cancer treatment, she gradually regained strength and energy and is now free of daily medications: "I had forgotten what it was to be me," she said.

Allie Rubin, 60, of Florida, who battled lupus for decades, qualified for CAR-T when she developed lymphoma. After a challenging recovery from a serious side effect, she is approaching two years without signs of either cancer or lupus.

How CAR-T and "living drugs" work

CAR-T was originally developed to treat certain blood cancers by reprogramming a patient’s T cells to destroy malignant B cells. Researchers have adapted this idea for autoimmune diseases in which B cells (the antibody-producing cells) play a harmful role. In the experimental autoimmune approach, doctors collect a patient’s T cells, engineer them in a lab to target B cells, then infuse millions of these modified "living drugs" back into the patient after brief chemotherapy.

Early reports from Germany and other centers have shown striking remissions in some patients with refractory lupus, myositis, scleroderma and other disorders, prompting a surge of clinical trials worldwide. Investigators theorize that deep depletion of problematic B cells can "reboot" the immune system so newly formed B cells are healthy.

Alternative and off-the-shelf strategies

Because individualized CAR-T is complex, time-consuming and expensive (cancer CAR-T treatments can cost roughly $500,000), companies are developing off-the-shelf CAR-T made from donor cells. Other strategies repurpose cancer tools that don't require custom cell engineering, such as T cell engager antibodies ("matchmakers" that redirect a patient’s existing T cells to target harmful B cells). Early reports of teclistamab, a T cell engager, showed significant improvement and drug-free remissions for several patients in a small series.

Regulatory T cells, mRNA and next-generation precision

Some researchers focus on expanding or engineering regulatory T cells (the immune system’s "peacekeepers") to calm autoimmunity rather than killing cells outright. Others seek highly precise targeting: identifying the small population of "rogue" B cells by molecular "barcodes" and removing only those while sparing protective cells.

Another promising direction uses mRNA packaged in biodegradable nanoparticles to deliver instructions to immune cells (an approach inspired by COVID-19 vaccine technology). In laboratory models, teams aim to tell immune "generals" to suppress destructive cells and amplify regulatory cells, effectively retraining the immune system. Human studies of these mRNA-based approaches are still several years away.

Predicting and preventing disease

Prevention efforts are already emerging. Teplizumab, approved to delay the onset of type 1 diabetes in at-risk people, demonstrates that intervening before symptoms start can preserve function. Researchers are mapping early immune changes in people at risk for diseases such as rheumatoid arthritis to identify targets for similar preventive strategies.

Benefits, risks and the road ahead

These approaches have produced dramatic remissions in some patients, but they remain experimental. Key questions include long-term durability, safety (including potentially severe side effects), cost and scalability. CAR-T is the most advanced in trials, but all strategies require further testing across larger, diverse patient groups.

Researchers are cautiously optimistic. "We've never been closer to getting to — and we don't like to say it — a potential cure," said Dr. Maximilian Konig of Johns Hopkins. "I think the next 10 years will dramatically change our field forever."

Reporting reflects results and quotes from multiple early studies and interviews with clinicians and patients involved in experimental autoimmune therapy research.