Future of Chimeric Antigen Receptors (Cars): Could it Drive Solutions Beyond Cancer? Examples in Autoimmune Diseases

Español-Rego, Marta; Marzal, Berta; Llobell, Arturo; Maria, C. Ana; Boronat, Anna

doi:10.15406/moji.2017.05.00158

Cited by 3 publications

(5 citation statements)

References 23 publications

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“…The pathogenesis of AIDs is not clear, but according to current study, the breakage of immune tolerance demonstrated when B or T lymphocytes fail to distinguish self from nonself with involvement of autoantibodies and/or self-reactive T lymphocytes is related to AIDs [2,10]. The explanatory mechanisms to autoreactive B or T cells can be proposed as "molecular mimicry," the most common mechanism, which is when the sequence of pathogen-derived peptides is similar with self-peptides, which causes crossreactivity of antigen receptors and results in autoimmune response; "epitope spreading," caused by virus infection, which is the change from the primary epitope to other epitopes or the generation of multiple neoepitopes on antigenpresenting cells; "bystander activation" which means the activation of preexisting autoreactive immune cells; and "viral persistence and polyclonal activation," explained by…”

Section: Introduction Of Autoimmune Diseasesmentioning

confidence: 75%

“…6 Journal of Immunology Research For the use of CAR-Tregs, attention should be paid to several issues. On the on hand, the immunosuppressive phenotype of Tregs will change after losing Foxp3 expression under an inflammatory microenvironment, from the immunosuppressive state to effector cells that aggravate disease symptoms [10]. To maintain the immune inhibitory phenotype of Tregs, several methods can be tried, like treating the Tregs with the vitamin A derivative all-trans retinoic acid that can sustain the stability and functionality of Tregs [71], administrating a Treg-favoring microbiota to the gut [72], and inducing ectopic expression of the Foxp3 gene to a stable regulatory phenotype of Tregs [73].…”

Section: Future Prospectsmentioning

confidence: 99%

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Immunotherapy Deriving from CAR-T Cell Treatment in Autoimmune Diseases

Chen

Sun

Liu

et al. 2019

Journal of Immunology Research

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Chimeric antigen receptor T (CAR-T) cells are T cells engineered to express specific synthetic antigen receptors that can recognize antigens expressed by tumor cells, which after the binding of these antigens to the receptors are eliminated, and have been adopted to treat several kinds of malignancies. Autoimmune diseases (AIDs), a class of chronic disease conditions, can be broadly separated into autoantibody-mediated and T cell-mediated diseases. Treatments for AIDs are focused on restoring immune tolerance. However, current treatments have little effect on immune tolerance inverse; even the molecular target biologics like anti-TNFα inhibitors can only mildly restore immune balance. By using the idea of CAR-T cell treatment in tumors, CAR-T cell-derived immunotherapies, chimeric autoantibody receptor T (CAAR-T) cells, and CAR regulatory T (CAR-T) cells bring new hope of treatment choice for AIDs.

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Section: Introduction Of Autoimmune Diseasesmentioning

confidence: 75%

Section: Future Prospectsmentioning

confidence: 99%

Immunotherapy Deriving from CAR-T Cell Treatment in Autoimmune Diseases

Chen

Sun

Liu

et al. 2019

Journal of Immunology Research

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“…43 Importantly, CAR Tregs could differentiate into effector cells by losing their immunosuppressive phenotype under an inflammatory microenvironment, leading to aggravation of disease symptoms. 68 The patients selected for CAR T-cell therapy have been already treated with immunosuppressants and their risk of infections increased while on CAR T-cell infusions. Some patients with malignancies should receive substantial immunosuppression for acute management after CD19-targeted CAR-T-cell therapy.…”

Section: Car Tregs To Treat Autoimmune Encephalomyelitis (Eae)mentioning

confidence: 99%

“…However, the ongoing research attempts to improve the durability by improving patients selection, CAR designs, manufacturing process 43 . Importantly, CAR Tregs could differentiate into effector cells by losing their immunosuppressive phenotype under an inflammatory microenvironment, leading to aggravation of disease symptoms 68 . The patients selected for CAR T‐cell therapy have been already treated with immunosuppressants and their risk of infections increased while on CAR T‐cell infusions.…”

Section: Car T‐cell Therapy In Rheumatologymentioning

confidence: 99%

Expanding the role of CAR T‐cell therapy: From B‐cell hematological malignancies to autoimmune rheumatic diseases

Shumnalieva,

Velikova,

Monov

2024

Int J of Rheum Dis

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Chimeric antigen receptor (CAR) T‐cell therapy is a form of immunotherapy where the lymphocytes, mostly T‐cells, are redirected to specifically recognize and eliminate a target antigen by coupling them with CARs. The binding of CAR and target cell surface antigens leads to vigorous T cell activation and robust anti‐tumor immune responses. Areas of implication of CAR T‐cell therapies include mainly hematological malignancies (i.e., advanced B‐cell cancers); however, recent studies have proven the unprecedented success of the new immunotherapy also in autoimmune rheumatic diseases. We aim to review the recent advances in CAR T‐cell therapies in rheumatology but also to address the limitations of their use in the real clinical practice based on the data on their efficacy and safety.

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“…These drugs include TNF-a inhibitors, belimumab and rituximab depleting B cells, T-cell costimulation blocker, anti-interleukin 6 (IL-6), anti-IL-1, and protein kinase inhibitors (16). In addition, monoclonal antibodies (mAbs), such as anti-TNFa, anti-CD19, anti-CD20, anti-CD22, and anti-IL6R, target multiple B cell subtypes, and other aberrant cells in autoimmune diseases (17,18).…”

Section: Introductionmentioning

confidence: 99%

Chimeric Antigen Receptor Based Therapy as a Potential Approach in Autoimmune Diseases: How Close Are We to the Treatment?

et al. 2020

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Despite significant breakthroughs in understanding of immunological and physiological features of autoimmune diseases, there is currently no specific therapeutic option with prolonged remission. Cell-based therapy using engineered-T cells has attracted tremendous attention as a practical treatment for autoimmune diseases. Genetically modified-T cells armed with chimeric antigen receptors (CARs) attack autoreactive immune cells such as B cells or antibody-secreting plasma cells. CARs can further guide the effector and regulatory T cells (Tregs) to the autoimmune milieu to traffic, proliferate, and exert suppressive functions. The genetically modified-T cells with artificial receptors are a promising option to suppress autoimmune manifestation and autoinflammatory events. Interestingly, CAR-T cells are modified to a new chimeric auto-antibody receptor T (CAAR-T) cell. This cell, with its specific-antigen, recognizes and binds to the target autoantibodies expressing autoreactive cells and, subsequently, destroy them. Preclinical studies of CAR-T cells demonstrated satisfactory outcomes against autoimmune diseases. However, the lack of target autoantigens remains one of the pivotal problems in the field of CAR-T cells. CAR-based therapy has to pass several hurdles, including stability, durability, trafficking, safety, effectiveness, manufacturing, and persistence, to enter clinical use. The primary goal of this review was to shed light on CAR-T immunotherapy, CAAR-T cell therapy, and CAR-Treg cell therapy in patients with immune system diseases.

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Future of Chimeric Antigen Receptors (Cars): Could it Drive Solutions Beyond Cancer? Examples in Autoimmune Diseases

Cited by 3 publications

References 23 publications

Immunotherapy Deriving from CAR-T Cell Treatment in Autoimmune Diseases

Immunotherapy Deriving from CAR-T Cell Treatment in Autoimmune Diseases

Expanding the role of CAR T‐cell therapy: From B‐cell hematological malignancies to autoimmune rheumatic diseases

Chimeric Antigen Receptor Based Therapy as a Potential Approach in Autoimmune Diseases: How Close Are We to the Treatment?

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