The Fourth International Workshop on Clinical Transplant Tolerance.
clinical research/practice
clinical trial
immune regulation
immunosuppression/immune modulation
kidney transplantation/nephrology
liver transplantation/hepatology
tolerance: chimerism
tolerance: clinical
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
21
02
2020
revised:
20
05
2020
accepted:
08
06
2020
pubmed:
13
6
2020
medline:
22
6
2021
entrez:
13
6
2020
Statut:
ppublish
Résumé
The International Workshop on Clinical Transplant Tolerance is a biennial meeting that aims to provide an update on the progress of studies of immunosuppression minimization or withdrawal in solid organ transplantation. The Fourth International Workshop on Clinical Tolerance was held in Pittsburgh, Pennsylvania, September 5-6, 2019. This report is a summary of presentations on the status of clinical trials designed to minimize or withdraw immunosuppressive drugs in kidney, liver, and lung transplantation without subsequent evidence of rejection. All protocols had in common the use of donor or recipient cell therapy combined with organ transplantation. The workshop also included presentations of mechanistic studies designed to improve understanding of the cellular and molecular basis of tolerance and to identify potential predictors/biomarkers of tolerance. Strategies to enhance the safety of hematopoietic cell transplantation and to improve patient selection/risk stratification for clinical trials were also discussed.
Identifiants
pubmed: 32529725
doi: 10.1111/ajt.16139
pii: S1600-6135(22)08314-9
doi:
Substances chimiques
Immunosuppressive Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
21-31Subventions
Organisme : Wellcome Trust
ID : 211122/Z/18/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_18059
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L023784/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N027930/1
Pays : United Kingdom
Informations de copyright
© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.
Références
Scandling JD, Busque S, Dejbakhsh-Jones S, et al. Tolerance and withdrawal of immunosuppressive drugs in patients given kidney and hematopoietic cell transplants. Am J Transplant. 2012;12(5):1133-1145.
Scandling JD, Busque S, Shizuru JA, et al. Chimerism, graft survival, and withdrawal of immunosuppressive drugs in HLA matched and mismatched patients after living donor kidney and hematopoietic cell transplantation. Am J Transplant. 2015;15(3):695-704.
Busque S, Scandling JD, Lowsky R, et al. Mixed chimerism and acceptance of kidney transplants after immunosuppressive drug withdrawal. Sci Transl Med. 2020;12(528):eaax8863. https://doi.org/10.1126/scitranslmed.aax8863
Leventhal J, Abecassis M, Miller J, et al. Tolerance induction in HLA disparate living donor kidney transplantation by donor stem cell infusion: durable chimerism predicts outcome. Transplantation. 2013;95(1):169-176.
Leventhal JR, Elliott MJ, Yolcu ES, et al. Immune reconstitution/immunocompetence in recipients of kidney plus hematopoietic stem/facilitating cell transplants. Transplantation. 2015;99(2):288-298.
Leventhal A, Galvin J, Stare D, et al. Eight year follow-up of a phase 2 clinical trial to induce tolerance in living donor renal transplant recipients. Am J Transplant. 2017;17:276.
Kawai T, Cosimi AB, Spitzer TR, et al. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008;358(4):353-361.
Kawai T, Sachs DH, Sprangers B, et al. Long-term results in recipients of combined HLA-mismatched kidney and bone marrow transplantation without maintenance immunosuppression. Am J Transplant. 2014;14(7):1599-1611.
Kawai T, Sachs DH, Sykes M, Cosimi AB, Immune TN. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2013;368(19):1850-1852.
Farris AB, Taheri D, Kawai T, et al. Acute renal endothelial injury during marrow recovery in a cohort of combined kidney and bone marrow allografts. Am J Transplant. 2011;11(7):1464-1477.
Kawai T, Cosimi AB, Colvin RB, et al. Mixed allogeneic chimerism and renal allograft tolerance in cynomolgus monkeys. Transplantation. 1995;59(2):256-262.
Kawai T, Sogawa H, Boskovic S, et al. CD154 blockade for induction of mixed chimerism and prolonged renal allograft survival in nonhuman primates. Am J Transplant. 2004;4(9):1391-1398.
Yamada Y, Boskovic S, Aoyama A, et al. Overcoming memory T-cell responses for induction of delayed tolerance in nonhuman primates. Am J Transplant. 2012;12(2):330-340.
Yamada Y, Ochiai T, Boskovic S, et al. Use of CTLA4Ig for induction of mixed chimerism and renal allograft tolerance in nonhuman primates. Am J Transplant. 2014;14(12):2704-2712.
Levitsky J, Feng S. Tolerance in clinical liver transplantation. Hum Immunol. 2018;79(5):283-287.
Shaked A, DesMarais MR, Kopetskie H, et al. Outcomes of immunosuppression minimization and withdrawal early after liver transplantation. Am J Transplant. 2019;19(5):1397-1409.
Feng S, Ekong UD, Lobritto SJ, et al. Complete immunosuppression withdrawal and subsequent allograft function among pediatric recipients of parental living donor liver transplants. JAMA. 2012;307(3):283-293.
Feng S, Demetris AJ, Spain KM, et al. Five-year histological and serological follow-up of operationally tolerant pediatric liver transplant recipients enrolled in WISP-R. Hepatology. 2017;65(2):647-660.
Feng S, Bucuvalas JC, Demetris AJ, et al. Evidence of chronic allograft injury in liver biopsies from long-term pediatric recipients of liver transplants. Gastroenterology. 2018;155(6):1838-1851.e7.
Romano M, Fanelli G, Albany CJ, Giganti G, Lombardi G. Past, present, and future of regulatory T cell therapy in transplantation and autoimmunity. Front Immunol. 2019;10:43.
Bluestone JA, Buckner JH, Fitch M, et al. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci Transl Med. 2015;7(315):315ra189.
Levitsky J, Burrell BE, Kanaparthi S, et al. Immunosuppression withdrawal in liver transplant recipients on sirolimus. Hepatology. 2019. https://doi.org/10.1002/hep.31036
Todo S, Yamashita K, Goto R, et al. A pilot study of operational tolerance with a regulatory T-cell-based cell therapy in living donor liver transplantation. Hepatology. 2016;64(2):632-643.
Szabolcs P, Buckley RH, Davis RD, et al. Tolerance and immunity after sequential lung and bone marrow transplantation from an unrelated cadaveric donor. J Allergy Clin Immunol. 2015;135(2):567-570.
Szabolcs P. Cadaveric donor lung and bone marrow transplantation in immunodeficiency diseases. NIH Res Portfolio Online Report Tools.
Sawitzki B, Harden PN, Reinke P, et al. Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. Lancet. 2020;395(10237):1627-1639.
Fraser H, Safinia N, Grageda N, et al. A rapamycin-based GMP-compatible process for the isolation and expansion of regulatory T cells for clinical trials. Mol Ther Methods Clin Dev. 2018;8:198-209.
Group CSC, Haynes R, Harden P, et al. Alemtuzumab-based induction treatment versus basiliximab-based induction treatment in kidney transplantation (the 3C Study): a randomised trial. Lancet 2014;384(9955):1684-1690.
Mathew JM, H.-Voss J, LeFever A, et al. A phase I clinical trial with ex vivo expanded recipient regulatory T cells in Living Donor Kidney Transplants. Sci Rep. 2018;8(1);7428.
Dutt S, Baker J, Kohrt HE, et al. CD8+CD44(hi) but not CD4+CD44(hi) memory T cells mediate potent graft antilymphoma activity without GVHD. Blood. 2011;117(11):3230-3239.
Hongo D, Tang X, Baker J, Engleman EG, Strober S. Requirement for interactions of natural killer T cells and myeloid-derived suppressor cells for transplantation tolerance. Am J Transplant. 2014;14(11):2467-2477.
Hongo D, Tang X, Dutt S, Nador RG, Strober S. Interactions between NKT cells and Tregs are required for tolerance to combined bone marrow and organ transplants. Blood. 2012;119(6):1581-1589.
Hongo D, Tang X, Zhang X, Engleman EG, Strober S. Tolerogenic interactions between CD8(+) dendritic cells and NKT cells prevent rejection of bone marrow and organ grafts. Blood. 2017;129(12):1718-1728.
Kohrt HE, Pillai AB, Lowsky R, Strober S. NKT cells, Treg, and their interactions in bone marrow transplantation. Eur J Immunol. 2010;40(7):1862-1869.
Nador RG, Hongo D, Baker J, Yao Z, Strober S. The changed balance of regulatory and naive T cells promotes tolerance after TLI and anti-T-cell antibody conditioning. Am J Transplant. 2010;10(2):262-272.
Pillai AB, George TI, Dutt S, Strober S. Host natural killer T cells induce an interleukin-4-dependent expansion of donor CD4+CD25+Foxp3+ T regulatory cells that protects against graft-versus-host disease. Blood. 2009;113(18):4458-4467.
Spinner MA, Fernández-Viña M, Creary LE, et al. HLA-mismatched unrelated donor transplantation using TLI-ATG conditioning has a low risk of GVHD and potent antitumor activity. Blood Adv. 2017;1(17):1347-1357.
Muffly L, Sheehan K, Armstrong R, et al. Infusion of donor-derived CD8(+) memory T cells for relapse following allogeneic hematopoietic cell transplantation. Blood advances. 2018;2(6):681-690.
Meyer EH, Laport G, Xie BJ, et al. Transplantation of donor grafts with defined ratio of conventional and regulatory T cells in HLA-matched recipients. JCI Insight. 2019;4(10):e127244. https://doi.org/10.1172/jci.insight.127244
Pierini A, Iliopoulou BP, Peiris H, et al. T cells expressing chimeric antigen receptor promote immune tolerance. JCI Insight. 2017;2(20):e92865. https://doi.org/10.1172/jci.insight.92865
Bleakley M, Heimfeld S, Loeb KR, et al. Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts. J Clin Investig. 2015;125(7):2677-2689.
Tambur AR, Campbell P, Claas FH, et al. Sensitization in transplantation: assessment of risk (STAR) 2017 working group meeting report. Am J Transplant. 2018;18(7):1604-1614.
Wiebe C, Kosmoliaptsis V, Pochinco D, et al. HLA-DR/DQ molecular mismatch: a prognostic biomarker for primary alloimmunity. Am J Transplant. 2019;19(6):1708-1719.
Wiebe C, Rush DN, Nevins TE, et al. Class II eplet mismatch modulates tacrolimus trough levels required to prevent donor-specific antibody development. J Am Soc Nephrol. 2017;28(11):3353-3362.
Crossan C, Tsochatzis EA, Longworth L, et al. Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation. Health Technol Assess. 2015; 19(9):1-410.
Wood-Trageser MA, Lesniak AJ, Demetris AJ. Enhancing the value of histopathological assessment of allograft biopsy monitoring. Transplantation. 2019;103(7):1306-1322.
Dhaliwal HK, Hoeroldt BS, Dube AK, et al. Long-term prognostic significance of persisting histological activity despite biochemical remission in autoimmune hepatitis. Am J Gastroenterol. 2015;110(7):993-999.
Kelly D, Verkade HJ, Rajanayagam J, McKiernan P, Mazariegos G, Hubscher S. Late graft hepatitis and fibrosis in pediatric liver allograft recipients: current concepts and future developments. Liver Transpl. 2016;22(11):1593-1602.
Hubscher SG. What is the long-term outcome of the liver allograft? J Hepatol. 2011;55(3):702-717.
Wong T, Nouri-Aria KT, Devlin J, Portmann B, Williams R. Tolerance and latent cellular rejection in long-term liver transplant recipients. Hepatology. 1998;28(2):443-449.
Banff Working Group on Liver Allograft Pathology. Importance of liver biopsy findings in immunosuppression management: biopsy monitoring and working criteria for patients with operational tolerance. Liver Transpl. 2012;18(10):1154-1170.
Demetris AJ, Lunz JG 3rd, Randhawa P, Wu T, Nalesnik M, Thomson AW. Monitoring of human liver and kidney allograft tolerance: a tissue/histopathology perspective. Transpl Int. 2009;22(1):120-141.
Zachariah MS, Dwivedi AK, Yip CS, et al. Utility of serial protocol biopsies performed after 1 year in predicting long-term kidney allograft function according to histologic phenotype. Exp Clin Transplant. 2018;16(4):391-400.