The Emerging Role of Chimeric Antigen Receptor Therapies in the Treatment of Autoimmune Disorders
Scarlett Bloodworth
Background: Newly engineered chimeric antigen receptor T lymphocyte therapies have been successfully used in certain cancers, including leukemias and non-Hodgkin lymphoma.1 These CAR-T therapies are used to eradicate over-proliferating cells by programming cytotoxic T lymphocytes to induce apoptosis upon binding the B lymphocyte specific cell marker CD19.2 Though only CD19 specific therapies have been approved, chimeric antigen receptors can be synthesized to recognize and bind to any antigen, creating the potential for novel therapies against many conditions.2 Researchers have begun to test CAR therapies for autoimmune diseases, especially those which are mediated by autoreactive antibody production.
Research Objectives: The purpose of this literature review is to explore the emerging research which may support the application of CAR-T therapy outside of its currently approved application.
Methods: Using the PubMed search interface to identify relevant information within the Medline database, this researcher searched for publications concerning the application of chimeric antigen receptor therapies. Search terms included “autoimmune disease treatments,” “chimeric antigen receptor,” and “T lymphocyte autoimmune treatment.” Additional search terms included “autoantibody CAR T cell therapy,” “chimeric antigen receptor synthesis,” “anti-CD19 CAR T cell therapy,” and “autoimmune disease mechanisms.” Once relevant research was identified, additional studies were retrieved from cited and related studies.
Results: A study conducted by Oh, Mao, and Manfredo-Vieira, et al showed that a chimeric autoantigen receptor (CAAR) T cell therapy successfully induced complete remission of muscle specific tyrosine kinase myasthenia gravis in humanized mouse models, without identifiable off-target toxicity or related cytokine storm.3 Lee, Lundgren, Mao, et al successfully induced remission of mucosal pemphigus vulgaris in a humanized murine model using an anti-desmoglein-3 CAAR T therapy, with insignificant toxicity reactions.1 Another study showed subjective symptomatic and objective neurological improvement in ten patients with progressive multiple sclerosis using an anti-EBV CAR T lymphocyte infusion therapy.4 In a human trial, five patients with systemic lupus erythematosus achieved complete remission after receiving the currently approved CART19 therapy.2 Another study showed that CAR T cells designed to target citrullinated proteins eliminated autoreactive B cells associated with rheumatoid arthritis.5
Conclusions: Multiple studies have shown evidence that chimeric antigen receptor T lymphocyte therapies can be successfully utilized outside of the currently approved applications.5 Additional research is needed to determine the full application of these therapies outside of cancer treatments. Results from the aforementioned studies suggest CART therapies be introduced for human trial in autoimmune diseases, especially those mediated by autoreactive antibodies.
Works Cited:
- Lee J, Lundgren DK, Mao X, et al. Antigen-specific B cell depletion for precision therapy of mucosal pemphigus vulgaris. J Clin Invest. 2020;130(12):6317-6324. https://www.jci.org/articles/view/138416.Accessed Feb 17, 2023. doi: 10.1172/JCI138416.
- Mackensen A, Müller F, Mougiakakos D, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022;28(10):2124-2132. https://www.nature.com/articles/s41591-022-02017-5.Accessed Feb 17, 2023. doi: 10.1038/s41591-022-02017-5.
- Oh S, Mao X, Manfredo-Vieira S, et al. Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Nat Biotechnol. 2023:1-10. https://www.nature.com/articles/s41587-022-01637-z. Accessed Feb 5, 2023. doi: 10.1038/s41587-022-01637-z.
- Pender MP, Csurhes PA, Smith C, et al. Epstein-barr virus–specific T cell therapy for progressive multiple sclerosis. JCI Insight. 2018;3(22):e124714. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302936/.Accessed Mar 1, 2023. doi: 10.1172/jci.insight.124714.
- Zhang B, Wang Y, Yuan Y, et al. In vitro elimination of autoreactive B cells from rheumatoid arthritis patients by universal chimeric antigen receptor T cells. Annals of the Rheumatic Diseases. 2021;80(2):176-184. https://ard.bmj.com/content/80/2/176.Accessed Feb 17, 2023. doi: 10.1136/annrheumdis-2020-217844.