Chimeric antigen receptor (CAR) T-cell therapy is emerging as a promising treatment for autoimmune rheumatic diseases (ARDs). The most well-known ARDs are systemic lupus erythematosus (SLE, lupus), rheumatoid arthritis, scleroderma, Sjögren’s syndrome, ankylosing spondylitis, psoriatic arthritis, and juvenile idiopathic arthritis.
New research presented this month at the 2023 American College of Rheumatology’s annual meeting showed positive results for the long-term remission of treatment-resistant systemic lupus erythematosus utilizing this novel treatment!
You may be wondering,
Chimeric antigen receptor (CAR) T-cell therapy is an innovative and personalized form of immunotherapy used in the treatment of certain cancers and autoimmune diseases. It involves genetically modifying a patient’s own T-cells – a type of immune cell – to enhance their ability to target and destroy specific cells in the body.
The process can be broken down into five steps:
Generally, this is done by modulating the immune system’s response to target and eliminate cells responsible for autoimmune reactions. The CAR-T cells, equipped with the synthetic receptor, recognize and bind to cells expressing the target proteins associated with the autoimmune response. Once bound, the CAR-T cells activate the immune system to attack and eliminate the targeted autoimmune cells. By selectively targeting the cells involved in the autoimmune process, CAR-T therapy aims to dampen the abnormal immune response and potentially induce a state of remission for the autoimmune disease.
It is important to note that while CAR-T therapy certainly holds promise, it is still in the relatively early stages of development for autoimmune disease treatment. The approach needs careful refinement to minimize potential side effects and ensure that the treatment effectively targets the autoimmune response without causing harm to healthy tissues. Additionally, the safety and efficacy of CAR-T therapy for autoimmune diseases are subjects of ongoing research and clinical trials.
One should also note that “although the study results are encouraging, CAR-T cell therapy has several serious limitations including potentially life-threatening toxicities such as cytokine release syndrome (CRS, cytokine storm) and immune effector cell-associated neurotoxicity syndrome (ICANS). There is also the cost. In the United States, a single CAR-T infusion runs anywhere from $375,000 to $425,000. These prices do not take into account associated costs, which can be considerable. If the infusion is administered in a hospital, the hospital stay may cost as much as the infusion itself” (1).
Most recently, the pioneer of the method, Dr. Georg Schett, and his team at Friedrich Alexander University, reported success in achieving long-lasting complete remission in 15 autoimmune rheumatic disease (ARD) patients without compromising vaccine-induced immunities. This study followed up on the first-ever published study of CAR-T therapy for lupus, published by Schett in 2022.
Novartis has sponsored a Phase I/II study of its investigational CAR-T product, initially developed for chronic lymphocytic leukemia, in patients with severe treatment-resistant systemic lupus erythematosus (SLE, lupus). Their pilot study, which was mainly focused on the safety of the method, demonstrated effectiveness in three lupus patients. They hope to enroll 27 more lupus patients with an estimated completion date in late 2026.
Both approaches used CAR T-cell technology to induce temporary “deep depletion” of B cells responsible for autoantibody (antibodies produced by the immune system that attack an individual’s own proteins) production, and the Novartis efficacy data mirrored the Friedrich Alexander program, with autoantibody reduction and improved SLE Disease Activity Index scores.
The favorable outcomes support the need for future studies.
Ongoing global trials and increasing interest in CAR-T therapy for autoimmune disease are evident, with various entities exploring its potential. According to clinicaltrials.gov, at least 18 studies in active recruitment are being conducted in the United States and China as of today.
In the United States, the following studies are actively recruiting:
In China, the following studies are actively recruiting:
American College of Rheumatology. (2023 November 7). CAR-T Cell Therapy Leads to Long-Term Remission in Lupus while Maintaining Vaccine Response. https://rheumatology.org/press-releases/car-t-cell-therapy-leads-to-long-term-remission-in-lupus-while-maintaining-vaccine-response