Fundamentals of CAR T Cell Therapy and Its Investigational Use in Autoimmune Diseases Fundamentals of CAR T Cell Therapy and Its Investigational Use in Autoimmune Diseases

What is chimeric antigen receptor (CAR) T cell therapy?

Illustration of T cells with cell-surface receptors. — T cells shown with engineered receptors across the cell surface.

CAR T is an advanced cell therapy

that uses genetically engineered T cells to target specific cells in the body.^1-3 In the case of autologous CAR T cell therapy, a patient's own T cells are re-engineered in a laboratory to express a new receptor, known as a CAR.^2-4

Patient T cell plus chimeric antigen receptor equals CAR T cell. — CAR T cell therapy combines the specificity of an antibody with the cytotoxic and memory capabilities of a T cell.²

CAR T cell therapy

has been approved for patients with certain hematologic malignancies for many years.² It is now under investigation for patients with certain autoimmune diseases.⁵

Disclaimer: CAR T cell therapy is currently not approved in any autoimmune indications. The safety and efficacy of investigational therapies and/or uses have not been established.

Rationale for investigation of CAR T cell therapy in patients with autoimmune disease

Video preview showing CAR T-cell therapy as an investigational treatment for autoimmune diseases. — Video explaining the mechanism of action for CAR T cell therapy in autoimmune disease.

In autoimmune diseases, autoreactive B cells

proliferate and produce pathogenic autoantibodies and proinflammatory cytokines, leading to persistent inflammation, chronic disease activity, and progressive organ damage.⁵

Given that CD19 is broadly expressed across the B cell lineage,

CD19-directed CAR T cell therapy has the potential to induce deep B cell depletion,^5,8 including B cell populations in tissues and secondary lymphoid organs that are less accessible to other B cell–targeted therapies.⁵

Diagram comparing B cell depletion from CD20 monoclonal antibodies and CD19-directed CAR T cell therapy. — CD19-directed CAR T has been observed to deplete B cells in lymphoid tissues more completely than a CD20 monoclonal antibody^7-9* Complete B cell depletion has been observed across lymphoid and nonlymphoid tissues after CD19-directed CAR T cell therapy in patients with SLE and SSc.^8**

In Phase 1 studies, after CD19-directed CAR T cell infusion,

B cells were eliminated,^8,10* which may allow the adaptive immune system to reset. The B cell compartment reconstitutes and expands, with a primarily naive phenotype, functioning as an immune reset that may support recovery of normal immune function.⁵

*Additional studies are needed to confirm these findings.

This deep B cell depletion

with a CD19-directed CAR T cell therapy, may lead to durable responses in patients with autoimmune diseases and could ultimately shift treatment goals from suppression of disease activity with continuous therapy to sustained remission following a one-time treatment.⁵*

*Treatment process includes blood collection, CAR T cell manufacturing, administration, and adverse-effect monitoring.⁵

As of May 2026, preliminary data

from investigational CD19-directed CAR T cell therapy in autoimmune diseases have been presented in congress proceedings for ~300 patients, primarily with SLE, as well as SSc and IIM.^11-55 Follow-up across these datasets ranges from <1 month to ~5 years. Ongoing clinical trials include 18 active Phase 2 or 3 studies (including registrational studies) that will evaluate efficacy, durability of response (e.g. drug-free DORIS remission), immune reconstitution, optimal patient selection, and safety, including adverse events of interest with CAR T, such as CRS, ICANS, cytopenias, and infections.

Patients are closely monitored

by the CAR T cell treatment team for at least the first 2-4 weeks after infusion.⁵⁶

Disclaimer: Patient monitoring should occur in accordance with the applicable clinical trial protocol.

Monitoring and management of CAR T cell therapy adverse events of interest

CRS/ICANS^56-59

Category	Cytokine release syndrome (CRS)	Immune effector cell-associated neurotoxicity syndrome (ICANS)
Symptoms	Low grades (1-2): Low-grade fever/hypoxia High grades (3-4): Fever/hypoxia requiring treatment	Low grades (1-2): Decreased consciousness High grades (3-4): Stupor, seizure, cerebral edema
Management	Tocilizumab, corticosteroids, supportive care	Corticosteroids, supportive care

Other treatment-emergent adverse events⁶⁰

Category	Infections	Cytopenias
Types	Bacterial, viral, fungal infections	Neutropenia, thrombocytopenia, anemia, and/or leukopenia
Management	Prophylaxis against VSV/HSV and pneumonia Antibacterial or antifungal prophylaxis based on individual risk factors	Transfusion or growth factor support

Post CAR T infusion management

after the acute monitoring phase is a collaborative practice shared by the patient’s referring rheumatologist and the CAR T treatment team. It includes long-term safety and efficacy monitoring, immunologic assessment, and disease management.^56,57,60

The aim of ongoing research

is to continue evaluations and better understand patient selection, immune reconstitution, response and durability of response, safety outcomes, post-treatment monitoring, and quality-of-life measures.

Learn more about CAR T cell therapy research in autoimmune diseases

Learn more about ongoing clinical research

and how to connect patients with CAR T clinical trial sites through the resources below.

To learn more about CAR T cell therapy please visit https://www.cartautoimmune.com/

Visit

For information on BMS’s ongoing clinical trials in patients with autoimmune diseases please visit bmsclinicaltrials.com