Biopharmas developing CAR T therapies for autoimmune indications face major barriers to maximizing the market. Advances in the provider ecosystem and clinical infrastructure, as well as access and education, will be key to launching at scale.
The current standard of care for autoimmune diseases is generally effective at managing symptoms and sustaining a good quality of life, but cures are lacking. Enter CAR T cell therapies. While all seven existing CAR Ts have been approved for hematological malignancies, the field now has its sights set on the autoimmune area.
The CAR T cell therapy market stands to gain substantially. Autoimmune diseases are characterized by a higher prevalence of active patients than cancer, and the global market is estimated to be twice that of oncology.
But in my work as a strategic advisor at Beghou working with biopharma companies developing cell and gene therapies as well as those in the immunology space, I’ve identified major barriers to maximizing the market. For CAR T makers to reach that broad autoimmune market, several key factors are needed to drive success, from advances in the provider ecosystem and clinical infrastructure to new considerations for patients and payers.
CAR Ts for autoimmune full speed ahead
Data generated so far suggest that drug-free remission, once a distant dream, could become a reality for patients with certain autoimmune diseases. The potential to selectively dysregulate T cells or B cells and thus eliminate the need for chronic immunosuppression in systemic and organ-specific disease is very exciting.
To that end, the autoimmune area has become a very active one for CAR T research, with one 2025 estimate showing more than 119 registered clinical trials. R&D programs span many of the key B cell–mediated autoimmune diseases, from lupus and myasthenia gravis to multiple sclerosis and pemphigus vulgaris. The furthest along of these CAR Ts, Kyverna Therapeutics’ miv-cel (formerly KYV-101), is under FDA review for stiff person syndrome, while others are in earlier phases of clinical or preclinical testing.
Interim data from Phase 2 clinical trials for generalized myasthenia gravis presented last October demonstrated miv-cel’s potential to deliver durable, drug-free remission in this rare autoimmune neurological disorder as well.
Cabaletta Bio, meanwhile, presented data in May from the first four patients treated for pemphigus vulgaris, with the lowest dose of rese-cel. Without preconditioning, the CAR T therapy demonstrated consistent depletion of B cells and promising clinical activity.
Furthermore, Cartesian Therapeutics is running a Phase 2b trial for Descartes-08 in myasthenia gravis. Unlike standard CAR T, which involves permanent changes to cells’ DNA, this mRNA-based approach is temporary and controllable, aiming to reduce serious side effects.
These are just a few examples of the many investigational CAR T cell therapies being tested for autoimmune diseases. But for any of these promising therapies to make a difference in patients’ lives, the clinical workforce and infrastructure for delivering CAR Ts need to evolve. Rheumatologists must shift from a chronic therapy orientation toward a one-time treatment mindset, while the current cell-therapy infrastructure must scale up, from the number of hospital-based apheresis clinics to more community-based or outpatient infusion centers.
The provider ecosystem is not ready
The provider ecosystem—specifically in the field of rheumatology—will need to undergo a sea change to ensure widespread access, adoption and speedy delivery of CAR T therapies. Currently, rheumatologists are focused not on curing patients but on providing longitudinal care, nuanced immunomodulation and improved quality of life by managing disease. Shifting to a curative mindset, these specialists must collaborate with CAR T centers to establish clear guidelines on when to refer a patient as well as pre- and post-treatment protocols to reduce the anxieties of other stakeholders.
Education and cultural alignment will be important for rheumatologists and cell therapy specialists alike, as having CAR T as part of their treatment armamentarium will be a first for both. Rheumatologists will need to be clinically trained in the therapy in order to identify patients who can benefit from it. Cell therapy specialists must understand the nuances of autoimmune patients and disease management.
In addition, rheumatologists will need to be upskilled and trained in managing toxicity for these therapies. This requires a collaborative approach and shared protocols across specialties to prevent patients from being treated in silos.
Targeting the right patient population—refractory, high-risk or early aggressive phenotypes—will be important in clinical decision-making. Patients with these kinds of severe, treatment-resistant antibody-driven conditions will be most likely to benefit from CAR T therapy versus the standard of care, as current intervention strategies do not adequately control the underlying autoimmune process and thus do not induce long-term remission.
CAR T cells could potentially achieve this goal by deep depletion of B cells through the targeting of the surface molecule CD19. A landmark 2004 case series suggests that side effects of CD19 CAR T would be tolerable for autoimmune patients, showing that 15 patients with severe forms of three distinct autoimmune diseases (systemic lupus erythematosus, inflammatory myositis and systemic sclerosis) achieved drug-free remission, and only one patient in each disease group suffered manageable grade 2 cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome.
A clinical infrastructure paradigm shift
Just as infusion therapies in multiple sclerosis changed the treatment paradigm for the disease and created a need for infusion centers, CAR T would change the framework not only for how therapy is administered but also in the infrastructure required to scale. Initially there may be rheumatology/hematology hybrid centers, providing the opportunity to cross-train the workforce and act as force multipliers. As safety profiles simplify and preconditioning is eliminated, infusions will move to an outpatient setting. Eventually, the availability of these therapies may expand beyond oncology and rheumatology.
There is also the potential for hubs and spokes, with bigger academic centers/practices serving as hubs and smaller practices as feeder spokes to drive optimal patient care and the efficient use of infrastructure. Similar to airlines’ hub-and-spoke networks, the bigger academic centers could perform complex patient evaluations, handle product manufacturing (or act as the primary receiving site for commercial therapies) and oversee cryopreservation. They could also address acute, severe toxicities such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.
Spokes, meanwhile, could be the initial touchpoint for identifying eligible patients, performing initial clinical testing, collecting T cells via apheresis and infusing the engineered product. These facilities could also provide longitudinal follow-up and monitoring for adverse events and relapse. This kind of operating model provides seamless logistics at the hub level, reduced costs and a holistic and shared care approach along with decentralization of care with wider access for patients.
In vivo opens new frontiers
While traditional ex vivo CAR T therapies will require such innovation to expand their reach, the advent of in vivo therapies that reprogram immune cells directly within the body could further change how autoimmune diseases are treated.
In vivo CAR T will not require complex logistics, manufacturing and supply chains. Rather, T cells would be engineered within the body using targeted delivery vehicles such as viral vectors or lipid nanoparticles. By eliminating the manufacturing complexities of current CAR T therapies, in vivo treatment could be industrialized and scaled. These therapies could be administered in an outpatient setting with reduced wait times, lowering adoption barriers and opening new regions such as Asia-Pacific and Africa.
In vivo therapies are not without risks, however. These include off-target effects such as unintended cell transduction or ectopic gene expression that must be managed.
It is now clear that the autoimmune field is moving from suppression to precision re-engineering. And CAR T is just the start. Future approaches—such as in vivo options, gene editing and off-the-shelf cell therapies—may prove more scalable as autoimmune treatment undergoes a paradigm shift.
