• The potential of CAR T-cell therapy in the treatment of autoimmune diseases
  • Mitra Kiani,1,* Ghazal Emadian,2
    1. Regenerative Medicine Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
    2. Postgraduate student of Genetic, Genetic dept, Science faculty, Nourdanesh institute of higher education,Meymeh, isfahan, I.R. of Iran.


  • Introduction: Introduction: Autoimmune diseases arise when the immune cells malfunction and target the body’s native cells and tissues. Current medical interventions mostly rely on general immunosuppressants and interfering antibodies, which can help control the disease but rarely offer a cure. In several cases, CAR-T cell therapy represents a promising replacement for the dysfunction of the human immune system resulting from a disease. Chimeric Antigen Receptors (CARs) are synthetic molecules made by integrating an antigen-binding domain with one or more intracellular signaling regions of T cells, resulting from genetic transfer methods. The extracellular antigen-binding segment is connected to the transmembrane domain by a structural part described as the hinge or spacer, for which different kinds of its sequences, particularly those originating from CD28 and CD8, have been employed in CAR development. The primary generation of CARs was composed of a single-chain structure for external antigen recognition. However, these CAR T cells showed limited therapeutic effectiveness due to poor expansion and short persistence in the body. Second-generation CARs introduced a co-stimulatory signaling region—typically from CD28 or 4-1BB— placed between the transmembrane region and the CD3 domain. When both co-stimulatory domains are integrated and merged into one CAR structure, it is referred to as a third-generation CAR. Some researchers use the term "fourth-generation CARs" for construct components that amplify T cell function via secreting additional proteins, such as cytokines, or including extra elements like co-stimulatory ligands. It appears now that every structural part of a CAR affects its overall function, while even single amino acid substitutions generate profound outcomes, resulting in marked effects on antigen recognition thresholds, T cell exhaustion, and prolonged activity. In comparison to modified TCRs, CARs propose a broader functional range. While TCR signaling strength mainly depends on antigen-binding affinity, CARs influence a wider spectrum of T cell behavior .CAR T cells also offer unique therapeutic advantages: their accurate targeting outperforms that of most small-molecule drugs. Moreover, because they are living cells, a single CAR T cell can multiply rapidly and destroy hundreds or even thousands of target cells. This research focuses on the potential of CAR T cell therapy in the treatment of autoimmune diseases.
  • Methods: Methods: After searching Google Scholar and PubMed, we focused on exploring the role of CAR T cells in autoimmune disorders treatment. We used the keywords “CAR T cell,” in combination with “therapy,” and “Autoimmune disorders,” to refine our search. Based on our search objective and topic, we specifically selected articles dealing with clinical and laboratory studies. The articles we reviewed spanned the years 1998 to 2023. It is important to note that our categorization of articles was based on their findings, not organization by year.
  • Results: Results: Beyond modifying conventional T cells with CARs, regulatory T cells (Tregs)—a specialized T cell subset—can also be engineered to express CARs. The targets of the approach are to treat autoimmune conditions by sustaining immune balance and suppressing autoreactive responses through an antigen-specific mechanism. CAR-based therapies offer enhanced specificity and operate independently of HLA compatibility, helping them bypass various immune avoidance strategies used by pathogens and cancer cells, which often undermine traditional T cell therapies. Although CAR T cells are widely known for their success in oncology, the idea emerged originally from efforts to redirect T cells against HIV infection. At present, they are positioned to engage with a broad range of diseases and immunological dysfunctions. The definition of the “ideal” CAR T cell remains under discourse. A complicating factor in clinical studies is the patient-specific nature of CAR T products, as each is derived from an individual’s T cells. Clinical outcomes are frequently linked to the degree of CAR T cell proliferation, longevity, and the presence of memory-like characteristics. Thus, minimizing or delaying fatigue is a central goal of CAR T cell design. A key benefit of CAR T cells is their ability to recognize antigens without reliance on major histocompatibility complex (MHC), enabling broader applicability. Strategically directing CAR T cells during their development phase may unlock new therapeutic pathways for treating a variety of autoimmune disorders. Conclusion: Contemporary treatments for autoimmune diseases often fail to provide a cure, may induce significant side effects, and typically do not address all aspects of disease pathology. Consequently, transformative approaches like CAR T cell therapy are urgently required.
  • Conclusion: Conclusion: Contemporary treatments for autoimmune diseases often fail to provide a cure, may induce significant side effects, and typically do not address all aspects of disease pathology. Consequently, transformative approaches like CAR T cell therapy are urgently required.
  • Keywords: CAR T cell, Treatment, Chimeric antigen receptor, Immunotherapy, Autoimmune disorders