Donor-specific chimeric antigen receptor Tregs limit rejection in naive but not sensitized allograft recipients

Sicard, A; Lamarche, Caroline; Speck, Madeleine; Wong, May Q.; Rosado‐Sánchez, Isaac; Blois, M.-C. De; Glaichenhaus, Nicolas; Mahdavi, Majid; Levings, Megan K.

doi:10.1111/ajt.15787

Cited by 83 publications

(105 citation statements)

References 41 publications

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“…Additionally, HLA-A mismatching is commonly connected with the poor grafting result after transplantation ( 126 ). Some investigators have engineered anti-HLA-A2 CARs (A2-CARs) for Tregs, and also human A2-CAR-Tregs were assessed both in vitro and in vivo ( 139 – 143 ). All studies demonstrated the in vivo efficacy of CAR-Tregs in the prevention of human against mouse i.e.…”

Section: Role In Transplantationmentioning

confidence: 99%

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

et al. 2021

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Regulatory T cells (Tregs) are an immunosuppressive subgroup of CD4+ T cells which are identified by the expression of forkhead box protein P3 (Foxp3). The modulation capacity of these immune cells holds an important role in both transplantation and the development of autoimmune diseases. These cells are the main mediators of self-tolerance and are essential for avoiding excessive immune reactions. Tregs play a key role in the induction of peripheral tolerance that can prevent autoimmunity, by protecting self-reactive lymphocytes from the immune reaction. In contrast to autoimmune responses, tumor cells exploit Tregs in order to prevent immune cell recognition and anti-tumor immune response during the carcinogenesis process. Recently, numerous studies have focused on unraveling the biological functions and principles of Tregs and their primary suppressive mechanisms. Due to the promising and outstanding results, Tregs have been widely investigated as an alternative tool in preventing graft rejection and treating autoimmune diseases. On the other hand, targeting Tregs for the purpose of improving cancer immunotherapy is being intensively evaluated as a desirable and effective method. The purpose of this review is to point out the characteristic function and therapeutic potential of Tregs in regulatory immune mechanisms in transplantation tolerance, autoimmune diseases, cancer therapy, and also to discuss that how the manipulation of these mechanisms may increase the therapeutic options.

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Section: Role In Transplantationmentioning

confidence: 99%

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

et al. 2021

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“…Trials of CAR Tregs are planned by a number of commercial enterprises; therefore, the precise details of these studies are not publicly available. Nevertheless, while enthusiasm is justified, it is not yet entirely clear whether CAR Tregs are indeed effective in humans (or whether they will be active against memory responses [77]). Moreover, their production is further complicated by the need for complex genetic modification [78], making polyclonal Tregs an attractively simple proposition if their efficacy is confirmed.…”

Section: Regulatory T Cellsmentioning

confidence: 99%

Cellular therapies in organ transplantation

et al. 2021

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Summary Cellular therapy is a promising tool for improving the outcome of organ transplantation. Various cell types with different immunoregulatory and regenerative properties may find application for specific transplant rejection or injury‐related indications. The current era is crucial for the development of cellular therapies. Preclinical models have demonstrated the feasibility of efficacious cell therapy in transplantation, early clinical trials have shown safety of several of these therapies, and the first steps towards efficacy studies in humans have been made. In this review, we address the current state of the art of cellular therapies in clinical transplantation and discuss monitoring tools and endpoints for these studies.

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“…( 104 ) In another study, compared with irrelevant CAR Tregs, donor‐specific CAR Tregs significantly delayed rejection, diminished donor‐specific antibody (DSA) levels and frequencies of DSA‐secreting B cells, and had a weaker recall DSA response after skin transplantation in a mouse model, demonstrating antigen‐specific suppression. ( 105 ) These findings signal a promising direction for the development of CAR Treg therapies to induce antigen‐specific immune suppression after LT.…”

Section: Future Prospectsmentioning

confidence: 88%

Regulatory T Cell Therapy Following Liver Transplantation

Liu

et al. 2020

Liver Transpl.

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Liver transplantation (LT) is considered the gold standard of curative treatment for patients with end‐stage liver disease or nonresectable hepatic malignant tumors. Rejection after LT is the main nontechnical factor affecting the prognosis of recipients. Medical and surgical advances, combined with improved immunosuppression with drugs such as calcineurin inhibitors (CNIs), have contributed to an increase in 1‐year graft survival to around 80%. However, medium‐ and long‐term improvements in LT outcomes have lagged behind. Importantly, CNIs and other classical immunosuppressive drugs are associated with significant adverse effects, including malignancies, cardiovascular disease, and severe renal dysfunction. Immunomodulation using regulatory T cells (Tregs) is emerging as a promising alternative to classical immunosuppression. Since their discovery, the immunomodulatory effects of Tregs have been demonstrated in a range of diseases. This has rejuvenated the interest in using Tregs as a therapeutic strategy to induce immune tolerance after LT. In this review, we first summarize the discovery and development of Tregs. We then review the preclinical data supporting their production, mechanism of action, and therapeutic efficacy followed by a summary of relevant clinical trials. Finally, we discuss the outstanding challenges of Treg therapy and its future prospects for routine use in LT.

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Donor-specific chimeric antigen receptor Tregs limit rejection in naive but not sensitized allograft recipients

Cited by 83 publications

References 41 publications

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

Cellular therapies in organ transplantation

Regulatory T Cell Therapy Following Liver Transplantation

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