Chimeric Antigen Receptor T Cell (CAR-T) Therapies as a Novel Treatment for Autoimmune Diseases
- andrewrlook
- Sep 14
- 8 min read
What is CAR-T Therapy: An Introduction
Chimeric Antigen Receptor T Cell (CAR-T) Therapy is an emerging and exciting new therapeutic model currently used for treating cancer, namely blood cancers and other noncancerous bloodborne illnesses. Traditional treatments like surgery don't work with bloodborne illnesses, since liquid tumors cannot be surgically removed. Chemotherapy impacts every cell in your body, tumor and non-tumor, aiming to eliminate the cancer first. Comparatively, CAR-T treatment uses the body’s own immune system (T Cells) to target specific malignant cells and to avoid normal healthy cells. With CAR-T’s high prospects in cancer treatment, new research is emerging to expand and implement this treatment towards autoimmune conditions. [1][2][3][4][5]
How the Immune System Works: Antibodies and Antigens
One important facet of intercellular communication is accomplished using Antibody-Antigen recognition machinery. Antigens live on the surface of every cell, and serve the cell’s unique identifier, which differentiates things like harmful bacteria from Type A blood and everything in between. Antibodies, on the other hand, are antigen’s counterpart: each distinct Antibody is programmed to recognize one specific antigen. If Antibody “X” instead bumps into Antigen “X”, then the two proteins will bind, and a chemical reaction will occur. However, if Antibody “X” bumps into Antigen “Y”, nothing happens—this is the foundation of cell-specific intercellular chemical communication. [6]
The immune system has two important types of Leukocytes (white blood cells) called B Cells and T Cells that use this recognition machinery to help keep the body safe from infection. B Cell and T Cell antibodies are specifically programmed to pair with antigens from potentially harmful foreign entities such as bacteria or viruses. B Cells mass-produce antibodies and pump them into the bloodstream, whereas T Cells patrol the body with their antibodies on their cell surface. Regardless, both B Cells and T Cells function with the goal to find and remove anything that should not be in the body. As long as the antigen “key” finds its antibody “keyhole” (technically, the antibody is looking for an antigen, so the “keyhole” finds its “key”), the chemical reaction will occur. In the case of the B Cells and T Cells, the antibodies will mark the antigen and its corresponding cell and then summon the rest of the immune system to destroy the marked cell. [6]
Autoantibodies: What are Autoimmune Diseases?
B Cells and T Cells normally don’t recognize the body’s own native antigens, since their recognition machinery facilitates the marked cell’s destruction. However, when diseases like cancer hijack the body’s otherwise healthy cells, it can evade detection from the immune system by hiding behind the cell’s native antigens, allowing the hidden cancer to spread unimpeded and destroy the body from the inside out. Alternatively, genetic mutations can cause B Cells and T Cells to erroneously create Autoantibodies instead, which are antibodies that wrongfully recognize the body’s own antigens of healthy cells, mistakenly marking those healthy cells for destruction. The resultant disease from the body destroying itself is the molecular basis for many autoimmune diseases such as Type 1 Diabetes, Rheumatoid Arthritis, and Lupus. [3][4][5][7]
How are CAR-T Cells Made?
CAR-T Therapy utilizes this Antibody-Antigen machinery by genetically modifying T Cells to specifically target the hidden cancer cells or haywire immune cells creating autoantibodies. To create CAR-T Cells, T Cells are first harvested through a process called leukapheresis. Blood is removed from the body, similarly to dialysis; however, while dialysis removes the toxic materials in the blood, leukapheresis specifically removes leukocytes. Those harvested leukocytes are sorted, and the T Cells then have their surface receptors genetically modified into Chimeric Antigen Receptors (CAR), which are different components from different types of B Cells and T Cells that are mixed together to create a new custom chimeric T Cell that can target the cell responsible for the tumor or autoimmune disease. Specifically, components of CD3, CD4, CD8, and CD28 Cells are extracted and combined (other T Cell proteins and components are additionally added as needed, depending on the target disease). Once complete, the CAR-T Cells are reintroduced into the body to eliminate its target. [1][2][3][4][5]
CAR-T Therapy for Autoimmune Diseases: Type 1 Diabetes, Rheumatoid Arthritis, and Lupus
Currently, clinical trials are underway to see if we can use CAR-T to treat Type 1 Diabetes (T1D; also known as Insulin-Dependent Diabetes Mellitus or IDDM), Rheumatoid Arthritis (RA), and Systemic Lupus Erythematosus (Lupus or SLE). All of these autoimmune diseases currently have no cure—however, their mechanism of disease involves overactive B Cells that produce autoantibodies which attack healthy cells. CAR-T treatments generally involve targeting those mutated B Cells and removing the source of the autoantibody production. [3][4][5][8][9][10]
With T1D, a genetic mutation causes autoantibodies to mistakenly identify insulin-producing pancreatic β-cells as foreign entities. The pancreatic cells are then destroyed and no longer produce insulin, resulting in an insulin deficiency (this is distinct from Type 2 Diabetes, where the pancreatic cells produce insulin normally, but the body cannot properly use it). Current treatments supplant the deficient insulin with insulin injections, leading to life-long maintenance and daily injections. Using CAR-T therapy for T1D involves creating T1D-specific CAR-T Cells to target the B Cells creating those autoantibodies, removing the source of the deficiency by allowing the insulin-producing pancreatic β-cells to create insulin unimpeded. [8][11]
With RA, a genetic mutation causes autoantibodies to recognize various cells in your joints and produce an immune response, most notably a widespread inflammatory response. However, environmental factors also play a role in creating those autoantibodies and autoimmune response, similarly to allergies. Unfortunately, the exact environmental mechanisms are not fully known, and are currently the topic of further research. Current treatments involve using steroids and Disease-Modifying Anti-Rheumatic Drugs (DMARDs) to suppress the immune system and its subsequent inflammatory response, which has widespread adverse reactions and does not target autoantibodies. In comparison, CAR-T therapy customizes RA-specific CAR-T Cells to target the B Cells creating those autoantibodies, stopping the immune response and inflammation from occurring in the first place. [9][12]
With Lupus, multiple genetic mutations create multiple autoantibodies that can attack multiple organ systems, and introduce a myriad of inflammatory symptoms ranging from fever, joint pain, rashes, and issues with the lining of your skin and of your internal organs. Because Lupus manifests differently for every patient, there is no known identified common cause. Current treatments involve using corticosteroids, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), antimalarials, and other immunosuppressant and anti-inflammatory treatments to reduce overall inflammation, but those drug cocktails often have lots of adverse reactions. While the exact trigger for the rapid inflammation is not well known, it is known that certain B Cells are responsible for creating the autoantibodies. Therefore, using the specificity of CAR-T therapy, Lupus-specific CAR-T Cells can target the rampant B Cells and stop the inflammatory responses and alleviate symptoms. [10][13]
Benefits and Complications of CAR-T Therapy
Treatment results are proving to be long-lasting: the CAR-T Cells have their lifespans modified and extended much longer than normal T Cells to provide long-lasting effects. Many of the current clinical studies show promising results, with remission as long as five years and counting. Since this is a new and emerging treatment, these clinical studies are still working on observing the long-term effects of CAR-T therapy, both to monitor potential adverse reactions and total length of remission. With enough research and testing, we can hope to see CAR-T therapies expand beyond clinical trials and become approved for the general public as a standard treatment option. [3][4][5]
Unfortunately, while CAR-T treats the symptoms and stops the damage, whatever caused the B Cells to mutate and produce autoantibodies still remains and can reactivate at any time. While CAR-T may put a stop to flareups, it does not prevent B Cells from regenerating and creating more autoantibodies, leaving the disease ultimately uncured. Regardless, CAR-T treatments take an important step beyond previous treatments: by targeting the cells doing the damage and by clearing out the malignant cells from the body, we can alleviate symptoms, reduce side effects, and provide long-lasting relief, allowing scientists to develop new medicines to identify the root causes and develop cures. [1][2][3][4][5][9][10]
The CAR-T therapy itself is not without complications. Since CAR-T Therapy targets immune cells, destroying those immune cells commonly induces immunodeficiency, increasing susceptibility to infections, fevers, neurologic toxicities, and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) which describes a host of CAR-T Therapy-specific symptoms. Additionally, T Cells are unstable outside of the body, and can die during the genetic modification process. Furthermore, with all of the genetic edits made to the T Cell, the body’s immune system may no longer recognize the T Cells and may treat them as a foreign entity. Thus, there is a high risk for Cytokine Release Syndrome (CRS), where the immune system goes into overdrive, causing faintness, nausea, fever, fatigue, and more. As such, to allow the CAR-T Cells to properly assimilate, doctors have to temporarily suppress the immune system, oftentimes using drugs or chemotherapy, leading to even more immunodeficiency. As such, an important focus of current clinical trials and research is to reduce adverse reactions and improve CAR-T Cell procurement, production, and reintroduction into the body. [1][2][3][4][5][11][12][13]
CAR-T: An Individualized Alternative
With the successful prospects of CAR-T treatment for treating difficult cancers, its natural expansion into other difficult non-oncologic diseases is just beginning. With some time and willingness from patients and scientists alike, we can continue taking steps towards potentially curing previously incurable illnesses, one disease at a time.
References
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2. Wang, J., Wang, L. CAR-T cell therapy: Where are we now, and where are we heading?. Blood Science. 2023 Oct;5(4):237-48. doi: https://doi.org/10.1097/BS9.0000000000000173.
3. Zmievskaya, E., Valiullina, A., Ganeeva, I., et al. Application of CAR-T Cell Therapy beyond Oncology: Autoimmune Diseases and Viral Infections. Biomedicines. 2021 Jan 9;9(1):59. doi: https://doi.org/10.3390/biomedicines9010059.
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5. Li, YR., Lyu, Z., Chen, Y., Fang, Y., Yang, L. Frontiers in CAR-T cell therapy for autoimmune diseases. Trends in Pharmacological Sciences. 2024 Sep;45(9):839-57. doi: https://doi.org/10.1016/j.tips.2024.07.005.
6. Davies, D.R., Padlan, E.A., Sheriff, S. ANTIBODY-ANTIGEN COMPLEXES. Annual Review of Biochemistry. 1990 Jul;59:439-73. doi: https://doi.org/10.1146/annurev.bi.59.070190.002255.
7. Elkon, K., Casali, P. Nature and functions of autoantibodies. Nature Clinical Practice Rheumatology. 2008 Sep;4(9):491-8. doi: https://doi.org/10.1038/ncprheum0895.
8. Lucier, J., Mathias, P.M. Type 1 Diabetes.In StatPearls. StatPearls Publishing. Retrieved 2025 Jul 23 from https://www.ncbi.nlm.nih.gov/books/NBK507713/.
9. Chauhan, K., Jandu, J.S., Brent, L.H., Al-Dhahir, M.A. Rheumatoid Arthritis. StatPearls Publishing. Retrieved 2025 Jul 23 from https://www.ncbi.nlm.nih.gov/books/NBK441999/.
10. Justiz Vaillant, A.A., Goyal, A., Varacallo, M.A. Systemic Lupus Erythematosus. StatPearls Publishing. Retrieved 2025 Jul 23 from https://www.ncbi.nlm.nih.gov/books/NBK535405/.
11. Mohammadi, V., Maleki, A.J., Nazari, M. et al. Chimeric Antigen Receptor (CAR)-Based Cell Therapy for Type 1 Diabetes Mellitus (T1DM); Current Progress and Future Approaches. Stem Cell Reviews and Reports. 2024 Apr;20:585-600. doi: https://doi.org/10.1007/s12015-023-10668-1.
12. Bhandari, S., Bhandari, S., Bhandari, S. Chimeric antigen receptor T cell therapy for the treatment of systemic rheumatic diseases: a comprehensive review of recent literature. Annals of Medicine & Surgery. 2023 Jul;85(7):3512-8. doi: https://doi.org/10.1097/MS9.0000000000000891
13. Guffroy, A., Jacquel, L., Guffroy, B., Martin, T. CAR-T cells for treating systemic lupus erythematosus: A promising emerging therapy. Joint Bone Spine. 2024;91(5):105702. doi: https://doi.org/10.1016/j.jbspin.2024.105702.
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