Prospects of the Use of Cell Therapy to Induce Immune Tolerance

Wang, Zhenkun; Liu, Xiaolong; Cao, Fenglin; Bellanti, Joseph A.; Zhou, Jin; Zheng, Song Guo

doi:10.3389/fimmu.2020.00792

Cited by 18 publications

(15 citation statements)

References 143 publications

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“…1,2 Beyond effector T cells, regulatory T cells (Tregs, including CAR Tregs) have also been used to induce immune tolerance in the contexts of autoimmune diseases, graft-versushost disease, transplant rejection, and hypersensitivity reactions. 3,4 However, in all cases, the manufacture of clinically relevant, genetically modified CAR T cells is cumbersome and challenging. Cell preparation often takes several weeks, which restricts the use of this approach in patients with rapidly progressing disease.…”

Section: Introductionmentioning

confidence: 99%

A DL-4- and TNFα-based culture system to generate high numbers of nonmodified or genetically modified immunotherapeutic human T-lymphoid progenitors

Moirangthem

Lizot

et al. 2021

Cell Mol Immunol

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Several obstacles to the production, expansion and genetic modification of immunotherapeutic T cells in vitro have restricted the widespread use of T-cell immunotherapy. In the context of HSCT, delayed naïve T-cell recovery contributes to poor outcomes. A novel approach to overcome the major limitations of both T-cell immunotherapy and HSCT would be to transplant human T-lymphoid progenitors (HTLPs), allowing reconstitution of a fully functional naïve T-cell pool in the patient thymus. However, it is challenging to produce HTLPs in the high numbers required to meet clinical needs. Here, we found that adding tumor necrosis factor alpha (TNFα) to a DL-4-based culture system led to the generation of a large number of nonmodified or genetically modified HTLPs possessing highly efficient in vitro and in vivo T-cell potential from either CB HSPCs or mPB HSPCs through accelerated T-cell differentiation and enhanced HTLP cell cycling and survival. This study provides a clinically suitable cell culture platform to generate high numbers of clinically potent nonmodified or genetically modified HTLPs for accelerating immune recovery after HSCT and for T-cell-based immunotherapy (including CAR T-cell therapy).

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Section: Introductionmentioning

confidence: 99%

A DL-4- and TNFα-based culture system to generate high numbers of nonmodified or genetically modified immunotherapeutic human T-lymphoid progenitors

Moirangthem

Lizot

et al. 2021

Cell Mol Immunol

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“…Treg cells are central in the under-development tolerance-inducing cellular therapy. This therapy consists of the injection or implantation of living cells into a patient, with the potential to overcome the limitations of traditional drug treatment and to gain a deeper understanding of immune tolerance mechanisms [ 86 ]. Treg cell characterization through DNA methylation assessment is a crucial phase of these procedures, and TSDR methylation pattern has been studied in different kinds of patients to assess the suitability of these therapies.…”

Section: Discussionmentioning

confidence: 99%

The applications of DNA methylation as a biomarker in kidney transplantation: a systematic review

et al. 2022

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Background Although kidney transplantation improves patient survival and quality of life, long-term results are hampered by both immune- and non-immune-mediated complications. Current biomarkers of post-transplant complications, such as allograft rejection, chronic renal allograft dysfunction, and cutaneous squamous cell carcinoma, have a suboptimal predictive value. DNA methylation is an epigenetic modification that directly affects gene expression and plays an important role in processes such as ischemia/reperfusion injury, fibrosis, and alloreactive immune response. Novel techniques can quickly assess the DNA methylation status of multiple loci in different cell types, allowing a deep and interesting study of cells’ activity and function. Therefore, DNA methylation has the potential to become an important biomarker for prediction and monitoring in kidney transplantation. Purpose of the study The aim of this study was to evaluate the role of DNA methylation as a potential biomarker of graft survival and complications development in kidney transplantation. Material and Methods A systematic review of several databases has been conducted. The Newcastle–Ottawa scale and the Jadad scale have been used to assess the risk of bias for observational and randomized studies, respectively. Results Twenty articles reporting on DNA methylation as a biomarker for kidney transplantation were included, all using DNA methylation for prediction and monitoring. DNA methylation pattern alterations in cells isolated from different tissues, such as kidney biopsies, urine, and blood, have been associated with ischemia–reperfusion injury and chronic renal allograft dysfunction. These alterations occurred in different and specific loci. DNA methylation status has also proved to be important for immune response modulation, having a crucial role in regulatory T cell definition and activity. Research also focused on a better understanding of the role of this epigenetic modification assessment for regulatory T cells isolation and expansion for future tolerance induction-oriented therapies. Conclusions Studies included in this review are heterogeneous in study design, biological samples, and outcome. More coordinated investigations are needed to affirm DNA methylation as a clinically relevant biomarker important for prevention, monitoring, and intervention.

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“…The study of CAR-T mediated cytokine responses in chondrocytes may also contribute to the understanding of serious arthritis symptoms caused by CAR-T therapy, and more attention should be paid when CAR-T is used to treat bone metastases or bone cancer. In addition, while CII-CAR to be expressed on effector T cells can serve as a tool to study inflammation, the expression on regulator T cells might be used as a novel treatment for inflammatory arthritis (56,57).…”

Section: Discussionmentioning

confidence: 99%

Construction of CII-Specific CAR-T to Explore the Cytokine Cascades Between Cartilage-Reactive T Cells and Chondrocytes

et al. 2020

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Cytokine cascades exist in many autoimmune disorders which amplify and sustain the autoimmune process and lead to chronic inflammatory injury to the host tissues. Increasing evidence indicates that chondrocytes can interact with T cells, which may be a crucial event in inflammatory arthritis. To address the reciprocal influences of cartilage-reactive T cells and chondrocytes, we constructed cartilage-reactive T cells by developing a type II collagen-specific chimeric antigen receptor (CII-CAR). An in vitro co-culture model of CII-CAR-T cells and fresh cartilage was developed, in which CII-CAR-T displayed specific proliferative capacity and cytokine release against fresh cartilage samples, and chondrocytes could respond to CII-CAR-T cells by secreting IL-6. The proposed model will help us to explore the possible cytokine cascades between cartilage-reactive T cells and cartilage.

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Prospects of the Use of Cell Therapy to Induce Immune Tolerance

Cited by 18 publications

References 143 publications

A DL-4- and TNFα-based culture system to generate high numbers of nonmodified or genetically modified immunotherapeutic human T-lymphoid progenitors

A DL-4- and TNFα-based culture system to generate high numbers of nonmodified or genetically modified immunotherapeutic human T-lymphoid progenitors

The applications of DNA methylation as a biomarker in kidney transplantation: a systematic review

Construction of CII-Specific CAR-T to Explore the Cytokine Cascades Between Cartilage-Reactive T Cells and Chondrocytes

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