T cells expressing chimeric antigen receptor promote immune tolerance

Pierini, Antonio; Iliopoulou, Bettina P.; Peiris, Heshan; Pérez-Cruz, Magdiel; Baker, Jeanette; Hsu, Katie; Gu, Xueying; Zheng, Pingping; Erkers, Tom; Tang, Sai-Wen; Strober, William; Álvarez, Maite; Ring, Aaron M.; Velardi, Andrea; Negrin, Robert S.; Kim, Seung K.; Meyer, Everett

doi:10.1172/jci.insight.92865

Cited by 83 publications

(73 citation statements)

References 53 publications

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“…209 Together, these findings indicate that CAR Tregs may have a great therapeutic potential in transplantation. 209 Together, these findings indicate that CAR Tregs may have a great therapeutic potential in transplantation.…”

Section: Regulatory Immune Cell Infusionsmentioning

confidence: 90%

“…Tregs have been shown to significantly prolong survival of allogeneic islets expressing the MHC I antigen H-2D d . 209 Together, these findings indicate that CAR Tregs may have a great therapeutic potential in transplantation.…”

Section: Regulatory Immune Cell Infusionsmentioning

confidence: 90%

“…202 In their study, compared with polyclonal nTregs, A2-CAR Tregs exhibited a superior control of allospecific immune responses in vitro and in humanized mouse models. 209 Based on this approach, donor-specific H-2D d -mAbCAR 208 Furthermore, Antonio et al developed a new type of CAR termed mAbCAR expressing a FITC-targeted CAR on Tregs that could be activated in a flexible way by various mAbs covalently conjugated to FITC.…”

Section: Regulatory Immune Cell Infusionsmentioning

confidence: 99%

“…208 Furthermore, Antonio et al developed a new type of CAR termed mAbCAR expressing a FITC-targeted CAR on Tregs that could be activated in a flexible way by various mAbs covalently conjugated to FITC. 209 Based on this approach, donor-specific H-2D d -mAbCAR…”

Section: Regulatory Immune Cell Infusionsmentioning

confidence: 99%

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Impact of infection on transplantation tolerance

Luo

2019

Immunological Reviews

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Allograft tolerance is the ultimate goal of organ transplantation. Current strategies for tolerance induction mainly focus on inhibiting alloreactive T cells while promoting regulatory immune cells. Pathogenic infections may have direct impact on both effector and regulatory cell populations, therefore can alter host susceptibility to transplantation tolerance induction as well as impair the quality and stability of tolerance once induced. In this review, we will discuss existing data demonstrating the effect of infections on transplantation tolerance, with particular emphasis on the role of the stage of infection (acute, chronic, or latent) and the stage of tolerance (induction or maintenance) in this infection‐tolerance interaction. While the deleterious effect of acute infection on tolerance is mainly driven by proinflammatory cytokines induced shortly after the infection, chronic infection may generate exhausted T cells that could in fact facilitate transplantation tolerance. In addition to pathogenic infections, commensal intestinal microbiota also has numerous significant immunomodulatory effects that can shape the host alloimmunity following transplantation. A comprehensive understanding of these mechanisms is crucial for the development of therapeutic strategies for robustly inducing and stably maintaining transplantation tolerance while preserving host anti‐pathogen immunity in clinically relevant scenarios.

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Section: Regulatory Immune Cell Infusionsmentioning

confidence: 90%

Section: Regulatory Immune Cell Infusionsmentioning

confidence: 90%

Section: Regulatory Immune Cell Infusionsmentioning

confidence: 99%

Section: Regulatory Immune Cell Infusionsmentioning

confidence: 99%

See 2 more Smart Citations

Impact of infection on transplantation tolerance

Luo

2019

Immunological Reviews

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“…194 This is why a more specific therapy is being sought and the use of antigen-specific CAR Tregs is on the rise. 178,[195][196][197] This year, our group has shown for the first time the proof of concept that CD8 + CD45RC low/-Tregs expressing a CAR directed against HLA-A2 are significantly more suppressive on CD4 + and CD8 + effector T cell in vitro than polyclonal Tregs and are able to inhibit graft rejection and GVHD more effectively than polyclonal Tregs in vivo in a model of HLA-A2 + skin graft rejection and HLA-A2 + PBMC GVHD in NSG mice (manuscript submitted). Over the last 3 years, three groups have used anti-HLA-A2 antibody sequences to generate CARs and shown that anti-HLA-A2 CAR-transduced CD4 + Tregs in xeno-GVHD and skin grafts in NSG mice humanized with PBMCs had a higher suppressive potential than control CD4 + Tregs.…”

Section: Cd8 + Treg Clini C Al Trial In K Idne Y Tr An S Pl Anted Pmentioning

confidence: 99%

Future prospects for CD8⁺ regulatory T cells in immune tolerance

Flippe

Bézie

Anegón

et al. 2019

Immunological Reviews

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CD8+ Tregs have been long described and significant progresses have been made about their phenotype, their functional mechanisms, and their suppressive ability compared to conventional CD4+ Tregs. They are now at the dawn of their clinical use. In this review, we will summarize their phenotypic characteristics, their mechanisms of action, the similarities, differences and synergies between CD8+ and CD4+ Tregs, and we will discuss the biology, development and induction of CD8+ Tregs, their manufacturing for clinical use, considering open questions/uncertainties and future technically accessible improvements notably through genetic modifications.

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Regulatory T cells and transplantation tolerance: Emerging from the darkness?

Waldmann

2021

Eur J Immunol

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The field of tissue transplantation has revolutionized the treatment of patients with failing organs. Its success, thus far, has depended on combinations of immunosuppressive drugs that damp host immunity, while also imposing numerous unwanted side‐effects. There is a longstanding recognition that better treatment outcomes, will come from replacing these drugs, fully or in part, by taking advantage of tractable physiological mechanisms of self‐tolerance. The past 50 years have seen many advances in the field of self‐tolerance, but perhaps, the most tractable of these has been the more recent discovery of a subset T‐cells (Treg) whose role is to regulate or damp immunity. This article is intended to first provide the reader with some historical background to explain why we have been slow to identify these cells, despite numerous clues to their existence, and also to indicate how little we know about how they achieve their regulatory function in averting transplant rejection. However, as is often the case in immunology, the therapeutic needs often dictate that our advances move to translation even before detailed explanations of the science are available. The final part of the article will briefly summarize how Treg are being harnessed as agents to interface with or perhaps, replace current drug combinations.

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T cells expressing chimeric antigen receptor promote immune tolerance

Cited by 83 publications

References 53 publications

Impact of infection on transplantation tolerance

Impact of infection on transplantation tolerance

Future prospects for CD8⁺ regulatory T cells in immune tolerance

Regulatory T cells and transplantation tolerance: Emerging from the darkness?

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T cells expressing chimeric antigen receptor promote immune tolerance

Cited by 83 publications

References 53 publications

Impact of infection on transplantation tolerance

Impact of infection on transplantation tolerance

Future prospects for CD8+ regulatory T cells in immune tolerance

Regulatory T cells and transplantation tolerance: Emerging from the darkness?

Contact Info

Product

Resources

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Future prospects for CD8⁺ regulatory T cells in immune tolerance