Regulatory T cell (Treg)

About 1-2% of peripheral blood lymphocytes are Tregs. IPEX (immunodysregulation, polyhendocrinopathy, enteropathy, X-linked) syndrome is a severe Treg deficiency caused by mutations in a transcription factor controlling the Treg cell lineage. Reduced numbers or function of Tregs have been implicated in pathology for autoimmune diseases. Boosting Treg activity is a common goal being approached in the repurposing of drugs which enhance Treg function and also in Treg-based cell therapiescell therapies.

Hemophilia patients receiving factor VIIIfactor VIII (FVIII) replacement drugs can develop anti-drug antibodies. FVIII-specific Tregs (ANS8-CAR Tregs) have been shown to suppress anti-FVII antibody responses in mouse models.

CAR-Treg generation is based on technology used for CAR modified T cells (CAR-T) which are mainly used for cancer immunotherapies. The first two CAR-T cell therapies were approved by the US Food and Drug Administration in 2017 for the treatment of CD19+ B cell lymphomas. Clinical trials are testing the therapy for solid tumors. While the main function of killer T cells used in CAR-T cell therapycell therapy is to attack their target, such as cancer cells, Tregs function to protect their target from being attacked by immune system.

Cell therapies using Tregs are being developed to treat autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, inflammatory bowel disease, graft-versus-host disease (GvHD), which can occur after bone marrow transplant and organ transplant rejection. Adoptive cell therapy (ACT) treatments for non-immune diseases such as Alzheimer’s disease, Parkinson’s disease, heart disease and type 2 diabetes are also being investigated. Evidence is accumulating that non-immune diseases can be exacerbated by inflammation, and preclinical studies suggest Tregs may calm inflammation and reduce morbidity through tissue homeostasis and repair by producing epidermal growth factor receptor (EGFR) ligand amphiregulin. Results from a clinical trialclinical trial using Treg to treat amyotrophic lateral sclerosis indicate it may reduce disease progression. Tregs have been shown to increase bone marrow engraftment, decrease immune responses to gene therapy and facilitate would healing.

Cell therapies using Tregs are being developed to treat autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, inflammatory bowel diseaseinflammatory bowel disease, graft-versus-host disease (GvHD), which can occur after bone marrow transplant and organ transplant rejection. Adoptive cell therapy (ACT) treatments for non-immune diseases such as Alzheimer’s disease, Parkinson’s disease, heart disease and type 2 diabetes are also being investigated. Evidence is accumulating that non-immune diseases can be exacerbated by inflammation, and preclinical studies suggest Tregs may calm inflammation and reduce morbidity through tissue homeostasis and repair by producing epidermal growth factor receptor (EGFR) ligand amphiregulin. Results from a clinical trial using Treg to treat amyotrophic lateral sclerosis indicate it may reduce disease progression. Tregs have been shown to increase bone marrow engraftment, decrease immune responses to gene therapy and facilitate would healing.

CAR-Tregs are MHC-independent and are engineered with genes encoding chimeric antigen receptors. Chimeric antigen receptors (CARs) Chimeric antigen receptors (CARs) generally consist of a single-chain variable fragment which is a site for binding a monoclonal antibody, an extracellular hinge, a transmembrane region and intracellular signaling domains.

CAR-Treg therapy, where the CAR is targeted to HLA-A2, found on leukocytes emigrating from a transplant graft, could increase transplantation tolerance. This strategy shows promise in graft-versus-host disease mouse models. A2-CAR-Tregs have been developed to prevent rejection of skin allograft in humanized mouse models.

A FITC-targeted CAR on Tregs called mAb-directed CAR (mAbCAR) allows Tregs to be activated in a controllable way using various monoclonal antibodies (mAbs) that are covalently conjugated to FITC. The mAbCARs could be targeted to specific tissue sites to mitigate graft-versus-host disease.

TNP-CAR Tregs target an antigen commonly used in a mouse model of colitis, 2,4,6-trinitrophenol. Research in mouse models show this immunotherapy treatment may be protective against the disease and TNP-CAR Tregs localized to inflamed colonic mucosa.

MOG-CAR Tregs which target myelin oligodendrocyte glycoprotein (MOG) have been shown in mouse multiple sclerosis models to suppress autoimmune encephalomyelitis (EAE).

CEA-CAR Tregs have been shown to target lung epithelia in a mouse model of allergic asthma and reduce airway hyperactivity and reduce eosinophilic airway inflammation.

Hemophilia patients receiving factor VIII (FVIII) replacement drugs can develop anti-drug antibodies. FVIII-specific Tregs (ANS8-CAR Tregs) have been shown to suppress anti-FVII antibody responses in mouse models.

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Tregs engineered to express transgenic TCRs specific for autoantigens like Factor IX in hemophilia, myelin oligodentrocyte glycoprotein in Multiple SclerosisMultiple Sclerosis (MS) and pancreatis islet-specific antigens in type 1 diabetes are being researched at the preclinical stage. Some approaches combine antigen receptor engineering with control of cell differentiation. Tregs are not a terminally differentiated cell population are able to acquire the phenotype of effector T cells similar to T helper cells and are categorized into different subsets of T helper-like Tregs.

CAR-Treg generation is based on technology used for CAR modified T cells (CAR-T) which are mainly used for cancer immunotherapies. The first two CAR-T cell therapies were approved by the US Food and Drug Administration in 2017 for the treatment of CD19+ B cell lymphomas. Clinical trials are testing the therapy for solid tumors. While the main function of killer T cells used in CAR-T cell therapy is to attack their target, such as cancer cellscancer cells, Tregs function to protect their target from being attacked by immune system.

About 1-2% of peripheral blood lymphocytes are Tregs. IPEX (immunodysregulation, polyhendocrinopathy, enteropathy, X-linked) syndrome is a severe Treg deficiency caused by mutations in a transcription factor controlling the Treg cell lineage. Reduced numbers or function of Tregs have been implicated in pathology for autoimmune diseasesautoimmune diseases. Boosting Treg activity is a common goal being approached in the repurposing of drugs which enhance Treg function and also in Treg-based cell therapies.

Tregs previously were referred to as suppressor cells and they were initially isolated based on multiple cell surface markers such as CD4CD4, CD25 and CD62L. Purified Tregs with these markers and FOXP3+ Tregs have been used in clinical trials to treat organ transplant rejection, GvHD, type 1 diabetes and autoimmune syndromes.

Tregs engineered to express transgenic TCRs specific for autoantigens like Factor IXFactor IX in hemophilia, myelin oligodentrocyte glycoprotein in Multiple Sclerosis (MS) and pancreatis islet-specific antigens in type 1 diabetes are being researched at the preclinical stage. Some approaches combine antigen receptor engineering with control of cell differentiation. Tregs are not a terminally differentiated cell population are able to acquire the phenotype of effector T cells similar to T helper cells and are categorized into different subsets of T helper-like Tregs.

Cell therapies using Tregs are being developed to treat autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, inflammatory bowel disease, graft-versus-host disease (GvHD), which can occur after bone marrow transplant and organ transplant rejection. Adoptive cell therapy (ACT) treatments for non-immune diseases such as Alzheimer’s disease, Parkinson’s disease, heart disease and type 2 diabetes are also being investigated. Evidence is accumulating that non-immune diseases can be exacerbated by inflammation, and preclinical studies suggest Tregs may calm inflammation and reduce morbidity through tissue homeostasis and repair by producing epidermal growth factor receptor (EGFR) ligand amphiregulin. Results from a clinical trial using Treg to treat amyotrophic lateral sclerosis indicate it may reduce disease progression. Tregs have been shown to increase bone marrow engraftment, decrease immune responses to gene therapy and facilitate would healing.

About 1-2% of peripheral blood lymphocytes are Tregs. IPEX (immunodysregulation, polyhendocrinopathy, enteropathy, X-linked) syndrome is a severe Treg deficiency caused by mutations in a transcription factor controlling the Treg cell lineage. Reduced numbers or function of Tregs have been implicated in pathology for autoimmune diseases. Boosting Treg activity is a common goal being approached in the repurposing of drugs which enhance Treg function and also in Treg-based ACTscell therapies.

ACTsCell therapies using Tregs are being developed to treat autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, inflammatory bowel disease, graft-versus-host disease (GvHD), which can occur after bone marrow transplant and organ transplant rejection. ACT treatments for non-immune diseases such as Alzheimer’s disease, Parkinson’s disease, heart disease and type 2 diabetes are also being investigated. Evidence is accumulating that non-immune diseases can be exacerbated by inflammation, and preclinical studies suggest Tregs may calm inflammation and reduce morbidity through tissue homeostasis and repair by producing epidermal growth factor receptor (EGFR) ligand amphiregulin. Results from a clinical trial using Treg to treat amyotrophic lateral sclerosis indicate it may reduce disease progression. Tregs have been shown to increase bone marrow engraftment, decrease immune responses to gene therapy and facilitate would healing.

CAR-Tregs are MHC-independent and are engineered with genes encoding chimeric antigen receptors. Chimeric antigen receptors (CARs) generally consist of a single-chain variable fragment which is a site for binding a monoclonal antibody, an extracellular hinge, a transmembrane region and intracellular signaling domains.

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