CAR Treg: A new approach in the treatment of autoimmune diseases

Beheshti, Seyedeh Ameneh; Shamsasenjan, Karim; Ahmadi, Majid; Abbasi, Batol

doi:10.1016/j.intimp.2021.108409

Cited by 25 publications

(11 citation statements)

References 177 publications

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“… 30 , 31 These findings have stimulated advances in the clinical development of adoptive cell therapy (ACT) and targeted therapies of Tregs in the clinic, and early clinical trial results report excellent clinical safety and efficacy. 32 , 33 , 34 , 35 , 36 , 37 , 38 Moreover, antigen‐specific Tregs 25 , 39 , 40 and chimeric antigen receptors, and in genome editing Tregs‐based therapy 41 , 42 , 43 , 44 , 45 exhibited potent benefits in autoimmunity and transplantation. Hence, the identification of specific Tregs as targets is of great clinical significance.…”

Section: Introductionmentioning

confidence: 99%

Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity

Jiang

Zhu

Wang

et al. 2022

MedComm

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CD4 + CD25 + regulatory T cells (Tregs), a subpopulation of naturally CD4 + T cells that characteristically express transcription factor Forkhead box P3 (FOXP3), play a pivotal role in the maintenance of immune homeostasis and the prevention of autoimmunity. With the development of biological technology, the understanding of plasticity and stability of Tregs has been further developed. Recent studies have suggested that human Tregs are functionally and phenotypically diverse. The functions and mechanisms of different phenotypes of Tregs in different disease settings, such as tumor microenvironment, autoimmune diseases, and transplantation, have gradually become hot spots of immunology research that arouse extensive attention. Among the complex functions, CD4 + CD25 + FOXP3 + Tregs possess a potent immunosuppressive capacity and can produce various cytokines, such as IL‐2, IL‐10, and TGF‐β, to regulate immune homeostasis. They can alleviate the progression of diseases by resisting inflammatory immune responses, whereas promoting the poor prognosis of diseases by helping cells evade immune surveillance or suppressing effector T cells activity. Therefore, methods for targeting Tregs to regulate their functions in the immune microenvironment, such as depleting them to strengthen tumor immunity or expanding them to treat immunological diseases, need to be developed. Here, we discuss that different subpopulations of Tregs are essential for the development of immunotherapeutic strategies involving Tregs in human diseases.

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Section: Introductionmentioning

confidence: 99%

Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity

Jiang

Zhu

Wang

et al. 2022

MedComm

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“…One of the alternative approaches to TCRs is the engineering of Treg cells to express a CAR specific for the desired antigen. CARs are synthesized proteins with combined extracellular antigen binding domains, so-called single chain fragment variable (scFv), and intracellular signaling domains ( 63 , 76 ). Preclinical studies in mice have demonstrated the promise of this strategy.…”

Section: Increasing the Stability And Efficiency Of Treg Cellsmentioning

confidence: 99%

The emerging role of regulatory cell-based therapy in autoimmune disease

et al. 2022

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Autoimmune disease, caused by unwanted immune responses to self-antigens, affects millions of people each year and poses a great social and economic burden to individuals and communities. In the course of autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, and multiple sclerosis, disturbances in the balance between the immune response against harmful agents and tolerance towards self-antigens lead to an immune response against self-tissues. In recent years, various regulatory immune cells have been identified. Disruptions in the quality, quantity, and function of these cells have been implicated in autoimmune disease development. Therefore, targeting or engineering these cells is a promising therapeutic for different autoimmune diseases. Regulatory T cells, regulatory B cells, regulatory dendritic cells, myeloid suppressor cells, and some subsets of innate lymphoid cells are arising as important players among this class of cells. Here, we review the roles of each suppressive cell type in the immune system during homeostasis and in the development of autoimmunity. Moreover, we discuss the current and future therapeutic potential of each one of these cell types for autoimmune diseases.

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“…CAR Treg cells function differently compared to CAR T cells. Instead of killing target cells, CAR Treg cells release anti-inflammatory cytokines upon antigen recognition and act as a protective shield, preventing further autoreactivity [ 187 ]. One challenge to this therapy is the ability of Treg cells to switch to inflammatory phenotypes, which would exacerbate autoreactivity instead of preventing it, although researchers are aware of and are addressing this possibility by inducing FoxP3 in different ways [ 188 , 189 , 190 ].…”

Section: Cars Beyond Cancermentioning

confidence: 99%

“…Currently, no CAR Treg studies have progressed to human clinical trials; however, mixed results have been published in in vitro and animal studies for a variety of autoimmune diseases [ 187 ]. The first use of CAR Tregs was by Elinav et al in a colitis mouse model with a CAR Treg specific for 2,4,6-trinitrophenol.…”

Section: Cars Beyond Cancermentioning

confidence: 99%

Alternative CAR Therapies: Recent Approaches in Engineering Chimeric Antigen Receptor Immune Cells to Combat Cancer

et al. 2022

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For nearly three decades, chimeric antigen receptors (CARs) have captivated the interest of researchers seeking to find novel immunotherapies to treat cancer. CARs were first designed to work with T cells, and the first CAR T cell therapy was approved to treat B cell lymphoma in 2017. Recent advancements in CAR technology have led to the development of modified CARs, including multi-specific CARs and logic gated CARs. Other immune cell types, including natural killer (NK) cells and macrophages, have also been engineered to express CARs to treat cancer. Additionally, CAR technology has been adapted in novel approaches to treating autoimmune disease and other conditions and diseases. In this article, we review these recent advancements in alternative CAR therapies and design, as well as their mechanisms of action, challenges in application, and potential future directions.

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CAR Treg: A new approach in the treatment of autoimmune diseases

Cited by 25 publications

References 177 publications

Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity

Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity

The emerging role of regulatory cell-based therapy in autoimmune disease

Alternative CAR Therapies: Recent Approaches in Engineering Chimeric Antigen Receptor Immune Cells to Combat Cancer

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