Identification, selection, and expansion of non-gene modified alloantigen-reactive Tregs for clinical therapeutic use
| Autor: | Matthew J. Bottomley, Fadi Issa, Joanna Hester, Kathryn J. Wood, Alaa Alzhrani |
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| Rok vydání: | 2020 |
| Předmět: |
Graft Rejection
0301 basic medicine Isoantigens CAR chimeric antigen receptor MDSCs myeloid-derived suppressor cells medicine.medical_treatment TSDR regulatory T cell-specific demethylated region T-Lymphocytes Regulatory Cell therapy DC dendritic cell Clinical trials 0302 clinical medicine GMP good manufacturing practice FACS fluorescence-activated cell sorting pTreg peripheral regulatory T cell APC antigen presenting cells hemic and immune systems Immunosuppression Regulatory T cells Tconv conventional T cell IDO indoleamine 2 3-dioxygenase Haematopoiesis surgical procedures operative medicine.anatomical_structure Transplantation Tolerance TCR-Treg TCR-transduced Treg Tr1 type 1 regulatory cells Regulatory T cell Cellular therapy Immunology Treg regulatory T cell polyTregs Mregs regulatory macrophages chemical and pharmacologic phenomena Biology Article polyTregs polyclonally-expanded Tregs Alloantigen-reactive Tregs CTLA-4 cytotoxic T-lymphocyte antigen 4 03 medical and health sciences Antigen Immune Tolerance medicine Animals Humans tTreg thymus-derived regulatory T cell Gene Immunosuppression Therapy Transplantation HLA human leukocyte antigen arTreg alloantigen reactive regulatory T cell iDCs immature DCs Clinical trial 030104 developmental biology TCR T-cell receptor GVHD graft vs host disease 030215 immunology |
| Zdroj: | Cellular Immunology |
| ISSN: | 0008-8749 |
| Popis: | Highlights • Tregs are a major focus of investigation in transplantation for immunosuppression minimisation. • Development of alloantigen-specific Tregs has the potential to improve efficacy and safety. • A number of methodologies for production exist including culture with donor alloantigen. • Clinical trials of polyclonal Treg therapy are now moving into Phase II and beyond. Transplantation is limited by the need for life-long pharmacological immunosuppression, which carries significant morbidity and mortality. Regulatory T cell (Treg) therapy holds significant promise as a strategy to facilitate immunosuppression minimization. Polyclonal Treg therapy has been assessed in a number of Phase I/II clinical trials in both solid organ and hematopoietic transplantation. Attention is now shifting towards the production of alloantigen-reactive Tregs (arTregs) through co-culture with donor antigen. These allospecific cells harbour potent suppressive function and yet their specificity implies a theoretical reduction in off-target effects. This review will cover the progress in the development of arTregs including their potential application for clinical use in transplantation, the knowledge gained so far from clinical trials of Tregs in transplant patients, and future directions for Treg therapy. |
| Databáze: | OpenAIRE |
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