UPMC Division of Rheumatology and Clinical Immunology Building Clinical Platform for Emerging Cellular Therapies in Autoimmune Diseases
January 21, 2026
A multidisciplinary initiative in the UPMC Division of Rheumatology and Clinical Immunology is establishing the infrastructure to bring cellular therapies for treating autoimmune diseases into the Division’s clinical armamentarium. Beginning with clinical trials of chimeric antigen receptor (CAR) T-cell therapy for idiopathic inflammatory myopathies (IIMs; myositis), the initiative is planned to eventually include additional autoimmune conditions and emerging cellular therapy platforms when viable candidates emerge and are a natural fit for the Division’s clinical infrastructure and patient populations.
This ongoing work with advanced cellular therapies is reflective of the Division’s existing clinical capabilities, Centers of Excellence, and research infrastructure in autoimmune conditions, but also of the scientific rationale and strategic need to try and overcome the limitations of conventional disease-modifying immunosuppressive regimens for myositis, lupus, and other conditions.
Even with the advances in biologic therapies over recent years, many patients with severe forms of myositis, lupus, vasculitis, and scleroderma remain refractory to current treatment options. Prolonged steroid exposure, chronic disease activity, and treatment-limiting toxicities of existing therapeutics continue to be significant clinical challenges in rheumatology. Cellular therapies, like CAR T, offer a fundamentally different approach to treatment and symptom control that are designed to reset the immune system rather than modulate its behavior longitudinally.
“Our goal is not to evaluate CAR T in isolation, but to create a clinical trial foundation and ultimately a clinical care program for a broader set of immune-modifying therapies,” says Dana Ascherman, MD, professor of medicine, Margaret Jane Miller Endowed Professorship for Arthritis Research, and chief of the Division of Rheumatology and Clinical Immunology. “This is a collaborative effort across all of our disease centers, and what we’re building now is meant to support the next decade and beyond of innovation.”
Coordinated Development Across the Division
The initiative to bring cellular therapy clinical trials into the Division began more than a year ago with the formation of a workgroup representing each of the Division’s clinical Centers of Excellence. Leaders of the project include:
- Rohit Aggarwal, MD, MS, professor of medicine and codirector of the UPMC Myositis Center
- Chester Oddis, MD, professor of medicine and codirector of the UPMC Myositis Center
- Jeremy Tilstra, MD, PhD, from the Lupus Center of Excellence
- Rachel Gordon, MD, PhD, assistant professor of medicine and director of the UPMC Sjögren’s Disease Center
- Sebastian Sattui, MD, MS, assistant professor of medicine and director of the UPMC Vasculitis Center
- Robert Lafyatis, MD, professor of medicine
- Robyn Domsic, MD, MPH, associate professor of medicine and clinical director of the UPMC and University of Pittsburgh Scleroderma Center
- Kathryn Torok, MD, associate professor of pediatrics and director of the Pediatric Systemic Scleroderma Clinic.
The workgroup has collaborated to assess potential clinical trial sponsors, evaluate existing protocols, and establish a consistent framework for trial participation and translational science within the Division for cellular therapy candidates.
Dr. Oddis has played a key role in the project to help develop the survey instrument and interface with potential trial sponsors as part of the vetting process, while Dr. Tilstra will serve as the site principal investigator for the initial pilot studies.
The goal is to ensure that as trials open across different diseases, the Division has a unified operational and scientific strategy.
“We’ve been very intentional about creating a shared model across programs rather than building this in isolation,” Dr. Aggarwal says. “The diseases may differ, but the infrastructure, safety protocols, and translational opportunities are closely aligned.”
To support trial sponsor selection, the workgroup created a standardized survey instrument to assess pharmaceutical companies’ experience in autoimmunity, cell product manufacturing platforms, and clinical trial design. The group also engaged colleagues at UPMC Hillman Cancer Center to align on infusion protocols, safety monitoring, and care coordination as the early phase of implementation with cellular therapies will be administered in partnership with the Division’s colleagues at UPMC Hillman.
Myositis as the Initial Disease Focus for Cellular Therapy Clinical Trials
The myositis program will lead the Division’s initial entry into cellular therapy clinical trials with two CD19-directed CAR T trials that Dr. Aggarwal and colleagues are working to finalize with industry sponsors. The decision reflects both the immunopathologic rationale for targeting B cells in certain myositis subtypes and the Myositis Center’s existing robust research and clinical trials experience.
“We’ve had strong momentum in clinical trials for years in our group, so when the opportunity arose to bring cellular therapies, and in this case, CAR T into the Division, we were in a good position to go forth,” Dr. Aggarwal says. “Our team has experience operationalizing new studies, and we were eager to help set the path forward for our Division in this clinical space.”
Once the trials are approved and activated, infusions will be delivered through UPMC Hillman’s cellular therapy program, while the Rheumatology Division will manage patient screening, rheumatologic oversight, longitudinal data collection, and overall trial management. The long-term goal is to build the full spectrum of clinical and research capabilities, including training, infusion protocols, patient monitoring, regulatory operations, and translational science within the UPMC Division of Rheumatology and Clinical Immunology, enabling the Division to independently deliver cellular therapies and conduct associated clinical trials without reliance on external infrastructure.
“Initially we will be working closely with our UPMC Hillman colleagues to deliver these therapies safely, particularly in terms of potential treatment-related toxicities of CAR T therapy, including cytokine release syndrome and neurotoxicity,” Dr. Aggarwal says. “But in the long term, our goal is to develop the internal capacity to manage these therapies start to finish entirely within our division, just as we did years ago when we first began to use rituximab in our patients on a regular basis.”
That earlier shift from a reliance on oncology for monoclonal antibody infusions to full internal control within rheumatology is a useful historical comparison. When agents like rituximab were first introduced into autoimmune care, rheumatology providers lacked the protocols, infrastructure, and nursing support needed to deliver them. Over time, that gap closed through training and investment in outpatient infusion services.
“We’ve done this before,” Dr. Aggarwal says. “We’ve gone from needing oncology to give our patients rituximab to managing that entirely ourselves. That’s the same trajectory we’re on now with cellular therapies like CAR T.”
A Mechanistic Rationale for Targeting B Cells and CAR T in Myositis
The biological rationale for B-cell–targeted CAR T-cell therapy in IIM is based on the role of autoreactive B cells and plasma cells in the pathogenesis of many myositis subsets. While rituximab depletes circulating CD20-positive B cells, it does not target long-lived plasma cells or tissue-resident B-cell compartments, which are often at work in ongoing disease activity despite treatment. By contrast, CD19 is expressed across a broader range of B-cell types, making it a more effective target for cell-based therapies that are designed to fully deplete the autoreactive cellular constituents.
“There’s strong interest in CAR T therapy because of its potential to access tissue-based niches where pathogenic B cells may persist,” Dr. Aggarwal says. “If we can achieve deeper, more complete depletion of the autoreactive compartment, it could translate into longer-lasting remission.”
This rationale was explored in a recent review article published in The Journal of Rheumatology in June 2025 for which Dr. Aggarwal was the senior author. In this review, titled “Role of CD19 Chimeric Antigen Receptor T Cell Therapy in Idiopathic Inflammatory Myopathies,” Dr. Aggarwal and colleagues map out the immunologic mechanisms driving disease in IIMs and describe how CD19-directed CAR T cells may provide clinical benefit by both eliminating autoreactive B cells and interrupting pathologic T-cell and B-cell interactions.
The review also discusses how trial design in rheumatology may need to adapt CAR T therapy to autoimmune indications, but more broadly how trials in the cellular therapy space must be constructed for optimal results in the world of autoimmune disorders.
These considerations include appropriate lymphodepletion strategies, long-term intravenous immunoglobulin support for patients with prolonged B-cell aplasia, and the development of monitoring protocols for treatment-related toxicities, which may present differently or follow different trajectories in autoimmune populations compared to cancer patients undergoing CAR T therapy.
Dr. Aggarwal and colleagues recommend selecting patients with seropositive, treatment-refractory disease who have failed at least three prior agents, with active muscle or lung involvement and high disease activity at baseline. They propose using a Total Improvement Score threshold of 40 or higher as a primary endpoint, along with steroid tapering and immunosuppressant withdrawal as secondary markers of durable response. Long-term follow-up should include relapse monitoring, immune reconstitution analysis, and careful documentation of B-cell recovery dynamics, with protocolized supportive care for those requiring extended IVIG.
“What we tried to do in that paper was bring together the immunologic reasoning and the clinical uncertainties,” Dr. Aggarwal says. “We know we can deplete B-cells with CAR T. What we’re still learning is what that means long-term in autoimmunity.”
As part of the upcoming CAR T trials that Dr. Aggarwal and colleagues are working to operationalize, the Division is also exploring how to incorporate translational endpoints, including biospecimen collection and immunologic profiling, to better understand mechanisms of the clinical responses seen in patients in the future.
Cellular Therapies and Treatment Paradigms Beyond CAR T
While CAR T therapy for myositis will be the initial therapeutic platform of cellular therapies in the Division, both Dr. Ascherman and Dr. Aggarwal stress CAR T will most certainly not be appropriate for all patients with myositis, or for all autoimmune disease states, just as is the case for cancer patients.
Manufacturing complexity, toxicity risks, and patient-specific factors will limit the scalability of CAR T in its current form. Because of this, the Division is already evaluating emerging and existing cellular therapies, including bispecific T-cell engagers and CAR NK platforms that may offer improved accessibility and simplified delivery.
“This is the kind of work we need to be doing if we want to move beyond the limits of traditional immunosuppression in autoimmunity,” Dr. Aggarwal says. “We are not replacing existing treatments. We’re adding a new category for patients who need it most. We are not focusing our efforts on CAR T, we are using it as a first test case to build a cellular therapies program for autoimmune disorders that is comprehensive, patient specific, and adaptable to future innovations.”
Further Reading
