This story was originally published by Knowable Magazine.
At age 49, Jan Janisch-Hanzlik’s multiple sclerosis was destroying her freedom to live the life she wanted. She gave up her energetic nursing job for a desk role. Frequent falls made her afraid to hold her grandchildren. She had to maneuver to a much bigger house to make room for the wheelchair she feared she might find yourself needing full-time.
Even one of the best available medication wasn’t improving Janisch-Hanzlik’s symptoms, and she or he nervous they’d only worsen. So when she learned a couple of trial of CAR T cell therapy on the University of Nebraska Medical Center in Omaha, near the town of Blair where she lives, she phoned the clinic every other month until they were able to enroll her as the primary patient.
Originally designed to focus on and wipe out cancer by reprogramming the patient’s immune cells, CAR T is now being offered to patients in a whole bunch of clinical trials for autoimmune conditions like multiple sclerosis, lupus, Graves’ disease, vasculitis, and plenty of others. The hope is that CAR T can duplicate the success it has demonstrated in a spread of blood cancers by hunting down and eliminating cells that focus on the self in autoimmune diseases. This is able to essentially reset the body’s defenses to a state just like the one which existed before the disease took hold.
But together with CAR T’s promise come risks, questions and challenges. There’s uncertainty about how well it is going to work for autoimmunity and the way long any advantages might last, in addition to what long-term unwanted effects might arise. Janisch-Hanzlik knew this when she sat all the way down to receive the experimental treatment on June 9, 2025; she felt a combination of hope and fear knowing that she could be spending the following week being monitored for unwanted effects including dangerous inflammation.
Along with her clinical expertise and desire to pioneer a brand new treatment, Janisch-Hanzlik’s two young grandchildren helped encourage her pursuit of a treatment with known risks and unsure advantages. Because multiple sclerosis has a genetic component, Janisch-Hanzlik knew that they’ve an elevated likelihood of going through the identical struggle she has. “I’d need to give you the option to say I did all the things that I possibly could to stop them, or anyone else, from having something like this,” she says.
From Cancer to Autoimmunity
The primary CAR T cancer treatment was approved by the Food and Drug Administration in 2017 for an aggressive type of leukemia. Since then, the powerful and intensive treatment has resulted in long-term remission for a lot of cancer patients.
The essential premise of CAR T is to activate the facility of key immune cells called T cells. T cells normally recognize other cells which were infected by a virus or bacterium, or are otherwise abnormal, and either destroy them or recruit other parts of the immune system to achieve this.
In CAR T for cancer, scientists engineer those T cells to specifically hunt and destroy malignant cells. The technology got its start when cancer researchers discovered methods to take out a patient’s own T cells, insert DNA instructions for a “chimeric antigen receptor,” or CAR, and put them back into the person’s circulation. The CAR, which sits on the T cell’s surface and latches on to a selected molecular partner on the surface of cancerous cells, prompts the T cell to attack.
Today, CAR T cells are mostly programmed to attack B cells, one other key immune player. B cells are normally responsible for making antibodies, but in certain blood cancers, they proliferate uncontrolled. By giving T cells a CAR that recognizes certainly one of a few molecules unique to the B cell surface, the cells are reprogrammed to seek out and eliminate those cancerous cells.
B cells are also the central problem in lots of autoimmune conditions: They mistakenly make antibodies against normal tissues as a substitute of against invading pathogens. In order CAR T began to succeed against B cell cancers, it didn’t take long for doctors to reason that CAR T therapy may additionally give you the option to wipe out bad B cells in individuals with autoimmunity.
A German team pioneered autoimmune CAR T in a girl with lupus, reporting positive results in 2021. Since then, that team and others have worked to translate the oncology success of CAR T to tackle a broad spectrum of autoimmune diseases.
“I feel it’s a game changer,” says Amanda Piquet, an autoimmune neurologist on the University of Colorado Anschutz in Aurora. Piquet is evaluating CAR T therapy for a rare and poorly understood autoimmune condition called stiff person syndrome, with symptoms including muscle stiffness and painful spasms. There isn’t a FDA-approved treatment. When she heard about an organization called Kyverna that was testing CAR T cell therapy within the syndrome, she thought it was “an ideal opportunity.”
The study she led, which reported preliminary results in December 2025, tested a single dose of CAR T in 26 people. Before the treatment, many participants struggled with a slow, mechanical gait, and 12 used assistive devices reminiscent of walkers and canes. Most patients were capable of walk faster by 16 weeks post-treatment, and eight not needed their assistive devices for brief distances. In April, the corporate reported that every one 26 patients, as of their last follow-up appointment 4 to 12 months out from the therapy, were not using another immunotherapies.
Risks and Uncertainties
Despite such striking results, reprogramming the immune system isn’t any easy matter. In early treatment of cancer patients, CAR T cells produced life-threatening unwanted effects, as outlined in a 2026 article within the Annual Review of Medicine. As CAR T cells attack their targets, the associated inflammation may cause symptoms like high fevers and low blood pressure. If that inflammation reaches the brain, it could possibly cause additional problems reminiscent of confusion and drowsiness.
Fortunately, physicians now have a decade’s price of experience recognizing and treating these problems. “They’re actually reversible and don’t cause long-term damage more often than not,” says Emily Littlejohn, a rheumatologist on the Cleveland Clinic.
Physicians and patients also must contend with decreased immunity as each a side effect of the treatment and its desired end result. In CAR T treatment, doctors typically use powerful chemotherapy drugs to temporarily reduce the body’s immune cell population to make room for the brand new, engineered cells, leaving patients temporarily immunosuppressed. And if the treatment works, it is going to decimate B cell populations. Patients might be vulnerable to infections for as much as a yr after treatment, says Littlejohn.
These effects are manageable with preventive antibiotics, antivirals, and vaccines. Patients also retain antibodies that their B cells made before the treatment, which offer residual protection for a couple of months. And for reasons that should not yet fully understood, CAR T seems to go away older B cells, which offer immune memory of past infections, intact in some cases. One study found that autoimmune patients treated with CAR T still made antibodies for diseases they’d been previously vaccinated against, like chicken pox and measles. These are signs that the treatment didn’t completely return the immune system to its factory settings.
When evaluating CAR T risk, it’s essential to think about that many existing treatments for autoimmune disease also suppress the immune system for so long as an individual takes them, experts note.
But there are other possible CAR T risks for autoimmune patients. In February, FDA officials published a paper endorsing CAR T’s potential in autoimmunity but warning of “unpredictable long-term toxicity.” CAR T treatment for cancer, the authors noted, has been linked to diverse long-term issues reminiscent of Parkinson’s disease. There have also been cases where the bioengineered cells themselves turned malignant, causing latest, T cell-based cancers.
Causing a secondary cancer could also be an appropriate risk when treating a life-threatening cancer, but probably not for autoimmunity, says Matt Lunning, medical director for gene and cellular therapy at Nebraska Medicine in Omaha. Tips on how to balance the chance between the impacts of an autoimmune disease, which might range widely in severity, and the difficult-to-quantify risk of future unwanted effects or cancers stays a significant open query.
Researchers are already working on second- and third-generation versions of CAR T that they expect to be safer for each cancer and autoimmunity. For instance, James Howard, a neuromuscular neurologist on the University of North Carolina at Chapel Hill, is testing a technology from an organization called Cartesian Therapeutics that encodes the CAR using molecules of mRNA, the short-lived genetic messenger utilized in Covid-19 vaccines, as a substitute of long-lasting DNA. The CAR T cells should wipe out B cells for less than so long as the mRNA persists, then lose their B cell-targeting abilities. With no likelihood for genetically modified T cells to loaf around long-term, there ought to be no cancer risk.
One other plus of Cartesian’s approach: Physicians infuse these T cells in sufficient numbers that they don’t need to breed within the patient’s body, which Howard thinks reduces risk for inflammation. In a recent trial, 15 individuals with autoimmune diseases received the Cartesian CAR T treatment; two-thirds saw their symptoms improve and none suffered long-term serious unwanted effects.
Treating CAR T Sticker Shock
Beyond unwanted effects, the opposite major challenge facing CAR T therapy is its price tag, which reaches a whole bunch of hundreds of dollars including hospital stays, cell engineering, and other expenses.
The treatment would likely be cheaper, and simpler, if scientists could eliminate the necessity for personalized engineering of every patient’s own cells and as a substitute use donor cells, or if they might cut out the step of engineering and growing the cells in a laboratory. Lunning says he’s eyeing up-and-coming procedures that might modify an individual’s T cells inside their very own body as a substitute of doing the genetic engineering in a lab.
Researchers are even farther together with a version of CAR T that uses healthy donors as a source of T cells. These could then be utilized by many patients in an “off-the-shelf” approach. It’s a way that has its own challenges, due to immune mismatch between donor and patient cells that might make them attack one another. This problem might be overcome with additional genetic modifications to the donated T cells that prevent recipient and donor systems from recognizing one another as foreign, says Bing Du, an immunologist at East China Normal University in Shanghai who’s amongst many researchers working on this approach. Du estimates a lab could make CAR T cells for greater than 1,000 patients from a single donor’s blood cells, at significant cost savings.
This type of off-the-shelf CAR T therapy is what Janisch-Hanzlik of Nebraska received, under Lunning’s care, in 2025. The study organizers at TG Therapeutics expect to finish their research in early 2029.
Janisch-Hanzlik ended up sailing through the follow-up without unwanted effects. A few months after the infusion, she was watching TV when she noticed she not needed special glasses to correct double vision. She began forgetting to bring her cane when moving about her house or going grocery shopping; she didn’t need it. Now, nearly a yr for the reason that treatment, she rarely falls and not requires a each day, three-hour nap. She recently enjoyed a visit to the Grand Canyon and appears forward to spending more time along with her grandchildren.
She does still have symptoms, including weakness in her right leg, numbness and tingling in her feet, and difficulty finding the fitting word when speaking. She asks her doctors in the event that they think she’s going to get well, stay the identical or worsen again.
“I even have been told so again and again, ‘We don’t know, you’re the primary. We’re just going to must wait and see,’” she says. “I definitely am thankful for day by day I even have.”
This text originally appeared in Knowable Magazine, an independent journalistic endeavor from Annual Reviews. Join for the newsletter.