The Immune System Reset
CAR T cell therapy rewired cancer treatment. Now it's coming for autoimmune disease — with real promise and real risk.
By The Bio-Longevity Desk
Jan Janisch-Hanzlik was 49 when multiple sclerosis forced her out of the nursing floor and into a desk job. She stopped carrying her grandchildren after too many falls. She moved into a larger house to accommodate a wheelchair she feared would become permanent. The best available medication wasn't working. [1] So she did what few patients ever do: she phoned a clinical trial clinic every other month until they agreed to enroll her as their first patient. [1]
On June 9, 2025, Janisch-Hanzlik sat down at Nebraska Medicine's Fred & Pamela Buffett Cancer Center in Omaha and received an infusion of genetically engineered T cells sourced not from her own body but from a healthy donor. [2] The therapy — allogeneic CAR T cell therapy — had previously been used by Nebraska Medicine hematologists to treat blood cancers. [2]
The logic behind the approach is straightforward, even if the biology is not. CAR T — short for chimeric antigen receptor T cell — works by extracting T cells, engineering them to carry a receptor that recognizes a specific molecular target, and reinfusing them so they hunt and destroy the designated cells. [1] The Food and Drug Administration approved the first CAR T cancer treatment in 2017 for an aggressive form of leukemia, and since then it has produced long-term remission for many cancer patients. [1] Now, the same machinery is being pointed at a different enemy.
B cells are the link that connects oncology to autoimmunity. In certain blood cancers, B cells proliferate out of control; in autoimmune conditions, they make antibodies against the body's own tissues instead of against pathogens. [1] Once CAR T demonstrated it could eliminate malignant B cells, it didn't take long for researchers to theorize it could do the same for misbehaving ones. [1] The field has been accelerating ever since.
What makes this moment feel different from previous waves of immune-modulating therapy is not simply the ambition — it is the specificity. Rather than suppressing the immune system wholesale and indefinitely, the premise here is targeted deletion followed by a clean slate. The question is whether the body actually delivers on that premise, and at what cost.
The evidence accumulating in clinical trials is striking enough to command attention. [1] Before the infusion, many participants had a slow, mechanical gait; 12 relied on walkers or canes. By 16 weeks post-treatment, most were walking faster, and eight no longer needed their assistive devices for short distances. [1] By April, Kyverna reported that all 26 patients, as of their last follow-up four to 12 months out, were no longer using any other immunotherapies. [1]
The Nebraska trial where Janisch-Hanzlik was treated takes a distinct approach. Rather than engineering cells from each individual patient — the autologous method — it uses donor-derived, "off-the-shelf" cells that can be prepared in advance and used across many patients. [2] Matt Lunning, the hematologist/oncologist who oversaw her infusion, noted that a year before Janisch-Hanzlik's treatment, Nebraska Medicine administered the first allogeneic CAR T therapy to a patient with lupus, with excellent results. [1]
Janisch-Hanzlik was discharged on June 16. A couple of months after the infusion, she noticed she no longer needed special glasses to correct double vision. She started forgetting to bring her cane when moving about her house or going grocery shopping; she didn't need it. Nearly a year since the treatment, she rarely falls and no longer requires a daily, three-hour nap. She recently took a trip to the Grand Canyon. [1]
Her story is not a cure narrative — she is careful to say that — but it is a data point that clinicians keep returning to. One patient's improvement can be dismissed as noise. A pattern across disease categories, trial sites, and therapy types is something harder to ignore.
The risk profile, however, is not negligible. In early CAR T cancer treatments, the therapy produced life-threatening side effects; as the engineered cells attack their targets, the resulting inflammation can cause high fevers and low blood pressure, and if it reaches the brain, confusion and drowsiness. [1] A 2026 article in the Annual Review of Medicine documented these early dangers. [1] Physicians now have a decade of experience managing them, and Emily Littlejohn, a rheumatologist at the Cleveland Clinic, says they are "certainly reversible and don't cause long-term damage most of the time." [1]
Less tractable are the unknowns. In February, FDA officials published a paper endorsing CAR T's potential in autoimmunity but warning of "unpredictable long-term toxicity." [1] CAR T treatment for cancer has been linked to long-term issues including Parkinson's disease, and there have been cases where the bioengineered cells themselves turned malignant, causing new T cell-based cancers. [1] Lunning frames the risk calculus plainly: causing a secondary cancer may be acceptable when treating a life-threatening malignancy, but probably not for autoimmunity. [1] How to weigh that against the progressive damage of a disease like MS — which can vary widely in severity — remains unresolved.
Researchers are developing next-generation versions intended to reduce those risks. James Howard, a neuromuscular neurologist at the University of North Carolina at Chapel Hill, is testing a technology from Cartesian Therapeutics that encodes the CAR using mRNA — the short-lived genetic messenger used in Covid-19 vaccines — rather than long-lasting DNA. [1] The engineered T cells should eliminate B cells only for as long as the mRNA persists, then lose their targeting ability, removing the risk of genetically modified cells persisting long-term. [1]
The off-the-shelf model, meanwhile, is advancing along a parallel track for cost reasons as much as clinical ones. Current CAR T prices reach hundreds of thousands of dollars when hospital stays, cell engineering, and ancillary expenses are included. [1]
There are also signs that CAR T's immune reset is more selective than feared. One study found that autoimmune patients treated with CAR T still produced antibodies for diseases they had previously been vaccinated against, like chicken pox and measles — evidence that the treatment did not completely erase immune memory of past infections. [1] Patients can be vulnerable to new infections for up to a year after treatment, but preventive antibiotics, antivirals, and vaccines help manage that window, says Littlejohn. [1]
The broader shift underway is conceptual as much as clinical. For decades, autoimmune disease management meant lifelong suppression — controlling a misfiring system rather than correcting it. What CAR T proposes is closer to a reboot: identify the source of the malfunction, eliminate it, and let the system rebuild. Whether that reboot holds, and for whom, is what the next few years of trials will determine.
Janisch-Hanzlik still has symptoms — weakness in her right leg, numbness and tingling in her feet, difficulty finding words when speaking. [1] When she asks her doctors whether she will improve, plateau, or regress, the answer is consistent. "I have been told so many times, 'We don't know, you're the first. We're just going to have to wait and see,'" she says. [1]
Her motivation for enrolling, she has explained, was not only personal. Because multiple sclerosis has a genetic component, Janisch-Hanzlik knew her grandchildren carry an elevated chance of the same diagnosis. "I would want to be able to say I did everything that I possibly could to prevent them, or anyone else, from having something like this," she says. [1] That calculation — accepting uncertain personal risk to generate data that might protect others — is the quiet engine of every early-phase trial.
The trial at Nebraska Medicine will run until at least early 2029. [1] The answers Janisch-Hanzlik's doctors cannot yet give her — will this last, will it spread to others, will the next version be safer and cheaper — are the same answers the field is now organized around finding. The immune system took decades to learn how to attack the self. Researchers are betting they can teach it, in a single infusion, to stop.