Immunotherapy Deriving from CAR-T Cell Treatment in Autoimmune Diseases

Chen, Yuehong; Sun, Jianhong; Liu, Huan; Yin, Geng; Xie, Qibing

doi:10.1155/2019/5727516

Cited by 37 publications

(28 citation statements)

References 75 publications

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“…Furthermore, new therapeutic options were established in cancer therapy using engineered T cell subsets ( 78 , 79 ). Whether these advantages are suitable for clinical application and could be transferred to chronic infections and autoinflammatory diseases is still a topic of research ( 80 ).…”

Section: Discussionmentioning

confidence: 99%

T Cell Repertoire During Ontogeny and Characteristics in Inflammatory Disorders in Adults and Childhood

et al. 2021

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Since the first day of life, a newborn has to deal with various pathogens from the environment. While passive immune protection is provided by diaplacental maternal antibodies, the development of cellular immunity is ongoing. A mature immune system should be able not only to defend against pathogens, but should also be able to differentiate between self- and non-self-antigens. Dysregulation in the development of cellular immunity can lead to severe disorders like immunodeficiency, autoimmunity and chronic inflammation. In this review, we explain the role of T cell immunity in antigen detection and summarize the characteristics of a mature TCR repertoire as well as the current state of knowledge about the development of the TCR repertoire in ontogenesis. In addition, methods of assessments are outlined, with a focus on the advantages and disadvantages of advanced methods such as next generation sequencing. Subsequently, we provide an overview of various disorders occuring in early childhood like immunodeficiencies, autoimmunity, allergic diseases and chronic infections and outline known changes in the TCR repertoire. Finally, we summarize the latest findings and discuss current research gaps as well as potential future developments.

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Section: Discussionmentioning

confidence: 99%

T Cell Repertoire During Ontogeny and Characteristics in Inflammatory Disorders in Adults and Childhood

et al. 2021

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“…Finally, for SLE, a phase I clinical trial will test the safety of CD19-CAR-T cells designed to deplete B cells (NCT03030976). In addition, CD19-CAR-T cells will be tested with or without an intracellular signaling CD137 domain ( 255 ).…”

Section: T Cell Therapymentioning

confidence: 99%

Emerging Therapeutics for Immune Tolerance: Tolerogenic Vaccines, T cell Therapy, and IL-2 Therapy

2021

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Autoimmune diseases affect roughly 5-10% of the total population, with women affected more than men. The standard treatment for autoimmune or autoinflammatory diseases had long been immunosuppressive agents until the advent of immunomodulatory biologic drugs, which aimed at blocking inflammatory mediators, including proinflammatory cytokines. At the frontier of these biologic drugs are TNF-α blockers. These therapies inhibit the proinflammatory action of TNF-α in common autoimmune diseases such as rheumatoid arthritis, psoriasis, ulcerative colitis, and Crohn’s disease. TNF-α blockade quickly became the “standard of care” for these autoimmune diseases due to their effectiveness in controlling disease and decreasing patient’s adverse risk profiles compared to broad-spectrum immunosuppressive agents. However, anti-TNF-α therapies have limitations, including known adverse safety risk, loss of therapeutic efficacy due to drug resistance, and lack of efficacy in numerous autoimmune diseases, including multiple sclerosis. The next wave of truly transformative therapeutics should aspire to provide a cure by selectively suppressing pathogenic autoantigen-specific immune responses while leaving the rest of the immune system intact to control infectious diseases and malignancies. In this review, we will focus on three main areas of active research in immune tolerance. First, tolerogenic vaccines aiming at robust, lasting autoantigen-specific immune tolerance. Second, T cell therapies using Tregs (either polyclonal, antigen-specific, or genetically engineered to express chimeric antigen receptors) to establish active dominant immune tolerance or T cells (engineered to express chimeric antigen receptors) to delete pathogenic immune cells. Third, IL-2 therapies aiming at expanding immunosuppressive regulatory T cells in vivo.

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“…Applying these principles to treatment of autoimmune disorders, chimeric autoantibody receptor T (CAAR-T) cells have been developed to target autoreactive B cells secreting autoantibodies. Pre-clinical studies have found efficacy in various animal models of autoimmune disorders including autoimmune encephalomyelitis, lupus and pemphigus ( 98 ). Thus CAR T cell therapy offers a novel and attractive treatment opportunity in MG.…”

Section: Chimeric Antigen Receptor—t (Car-t) Cell Therapymentioning

confidence: 99%

Novel Treatments in Myasthenia Gravis

2020

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Myasthenia gravis (MG) is the prototypical autoimmune disorder caused by specific autoantibodies at the neuromuscular junction. Broad-based immunotherapies, such as corticosteroids, azathioprine, mycophenolate, tacrolimus, and cyclosporine, have been effective in controlling symptoms of myasthenia. While being effective in a majority of MG patients many of these immunosuppressive agents are associated with long-term side effects, often intolerable for patients, and take several months to be effective. With advances in translational research and drug development capabilities, more directed therapeutic agents that can alter the future of MG treatment have been developed. This review focuses on the aberrant immunological processes in MG, the novel agents that target them along with the clinical evidence for efficacy and safety. These agents include terminal complement C5 inhibitors, Fc receptor inhibitors, B cell depleting agents (anti CD 19 and 20 and B cell activating factor [BAFF)]inhibitors), proteosome inhibitors, T cells and cytokine based therapies (chimeric antigen receptor T [CART-T] cell therapy), autologous stem cell transplantation, and subcutaneous immunoglobulin (SCIG). Most of these new agents have advantages over conventional immunosuppressive treatment (IST) for MG therapy in terms of faster onset of action, favourable side effect profile and the potential for a sustained and long-term remission.

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Immunotherapy Deriving from CAR-T Cell Treatment in Autoimmune Diseases

Cited by 37 publications

References 75 publications

T Cell Repertoire During Ontogeny and Characteristics in Inflammatory Disorders in Adults and Childhood

T Cell Repertoire During Ontogeny and Characteristics in Inflammatory Disorders in Adults and Childhood

Emerging Therapeutics for Immune Tolerance: Tolerogenic Vaccines, T cell Therapy, and IL-2 Therapy

Novel Treatments in Myasthenia Gravis

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