Chimeric Antigen Receptor (CAR) T-cell therapy has gained recognition for its success in treating certain cancers, particularly blood malignancies like lymphomas and leukemias. While initially developed for oncology, CAR-T therapy is now showing considerable promise as an emerging treatment for severe autoimmune diseases, offering a new path for patients who have not responded to conventional therapies.
How CAR-T Therapy Works for Autoimmune Conditions
CAR-T therapy engineers a patient’s T-cells to recognize and destroy specific cells involved in autoimmune disease. In many autoimmune conditions, B cells, which produce antibodies, mistakenly create “autoantibodies” that attack the body’s own healthy tissues. T-cells are genetically modified to express a Chimeric Antigen Receptor (CAR) on their surface. This CAR is designed to specifically bind to an antigen found on the surface of these problematic B cells.
The most common target for CAR-T therapy in autoimmune diseases is the CD19 protein, present on almost all B cells. Once modified CAR-T cells are reintroduced into the patient’s body, they circulate and seek out B cells expressing CD19. Upon binding to the CD19 antigen, the CAR-T cells activate and proliferate, releasing substances that induce the death of the targeted B cells. This targeted elimination of autoreactive B cells aims to “reset” the immune system, potentially leading to long-term remission.
Autoimmune Diseases Under Investigation
CAR-T therapy is being investigated for several severe autoimmune diseases where B cells play a central role. Systemic Lupus Erythematosus (SLE) is a prominent example, characterized by the immune system attacking various organs and tissues through autoantibody production. Clinical trials for SLE, including lupus nephritis (LN), are exploring CD19-targeted CAR-T cells to deplete the autoreactive B cells responsible for the disease’s progression. Early findings have shown sustained depletion of circulating B cells and the disappearance of self-directed autoantibodies in some patients.
Systemic Sclerosis (SSc), a connective tissue disease causing widespread hardening of the skin and internal organs, is another condition being investigated. In SSc, dysfunctional B cells contribute to fibrosis and inflammation. CAR-T therapy offers a potential strategy to eliminate these problematic B cells and halt disease progression. Myasthenia Gravis, an autoimmune disorder affecting muscle weakness, is also a focus of research, with some studies exploring anti-B cell maturation antigen (BCMA) CAR-T cells for B cell elimination.
What to Expect During CAR-T Therapy
Receiving CAR-T therapy for an autoimmune condition involves several distinct steps, beginning with the collection of a patient’s T-cells. This initial step, known as apheresis, is similar to blood donation: blood is drawn, T-cells are separated, and the remaining blood components are returned. This process typically takes several hours. The collected T-cells are then sent to a specialized laboratory for genetic modification.
In the laboratory, T-cells are genetically engineered to express the Chimeric Antigen Receptor (CAR) on their surface, a process often utilizing viral vectors to introduce the new genetic material. Following genetic modification, the engineered CAR-T cells are expanded in the lab, growing into millions of cells over several weeks to ensure a sufficient therapeutic dose. The expanded CAR-T cells are infused back into the patient, usually through a central venous catheter. Patients are then closely monitored for a period following the infusion to manage any immediate reactions and observe the therapy’s effects.
Considerations and Outlook for CAR-T in Autoimmune
While CAR-T therapy holds significant promise for autoimmune diseases, it also comes with important considerations, including potential side effects observed in cancer trials. Cytokine Release Syndrome (CRS) is a common and potentially severe inflammatory response caused by the rapid activation and expansion of CAR-T cells, leading to symptoms such as high fever and low blood pressure. Another potential side effect is immune effector cell-associated neurotoxicity syndrome (ICANS), which can manifest as confusion or seizures, often linked to CRS.
Research into CAR-T therapy for autoimmune conditions is largely in the clinical trial phase, with early findings showing encouraging results regarding feasibility, tolerability, and efficacy. B cell recovery after CAR-T therapy in autoimmune patients appears to occur more rapidly than in cancer patients, and the repopulated B cells often lack the self-directed antibodies that drive the autoimmune disease. This suggests a potential “immunological reset.” Despite the positive early outcomes, more long-term assessments are needed to fully understand the durability of remission and overall safety before CAR-T therapy becomes widely adopted for autoimmune treatments.