دورية أكاديمية
Five-year follow-up of a phase I trial of donor-derived modified immune cell infusion in kidney transplantation.
| العنوان: | Five-year follow-up of a phase I trial of donor-derived modified immune cell infusion in kidney transplantation. |
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| المؤلفون: | Schaier M; Department of Nephrology, Heidelberg University Hospital, Heidelberg, ;Germany.; TolerogenixX GmbH, Heidelberg, ;Germany., Morath C; Department of Nephrology, Heidelberg University Hospital, Heidelberg, ;Germany.; TolerogenixX GmbH, Heidelberg, ;Germany.; German Center for Infection Research, German Center for Infection Research (DZIF), Thematic Translational Unit (TTU)-Infections of the Immunocompromised Host (IICH), Partner Site Heidelberg, Heidelberg, ;Germany., Wang L; TolerogenixX GmbH, Heidelberg, ;Germany.; Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, ;Germany., Kleist C; Institute of Immunology, Heidelberg University Hospital, Heidelberg, ;Germany.; Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, ;Germany., Opelz G; Institute of Immunology, Heidelberg University Hospital, Heidelberg, ;Germany., Tran TH; Institute of Immunology, Heidelberg University Hospital, Heidelberg, ;Germany., Scherer S; Institute of Immunology, Heidelberg University Hospital, Heidelberg, ;Germany., Pham L; Institute of Immunology, Heidelberg University Hospital, Heidelberg, ;Germany., Ekpoom N; Institute of Immunology, Heidelberg University Hospital, Heidelberg, ;Germany., Süsal C; Institute of Immunology, Heidelberg University Hospital, Heidelberg, ;Germany.; Transplant Immunology Research Center of Excellence, Koç University, Istanbul, ;Türkiye., Ponath G; Department of Nephrology, Heidelberg University Hospital, Heidelberg, ;Germany.; TolerogenixX GmbH, Heidelberg, ;Germany., Kälble F; Department of Nephrology, Heidelberg University Hospital, Heidelberg, ;Germany., Speer C; Department of Nephrology, Heidelberg University Hospital, Heidelberg, ;Germany., Benning L; Department of Nephrology, Heidelberg University Hospital, Heidelberg, ;Germany., Nusshag C; Department of Nephrology, Heidelberg University Hospital, Heidelberg, ;Germany., Mahler CF; Department of Nephrology, Heidelberg University Hospital, Heidelberg, ;Germany., Pego da Silva L; Department of Nephrology, Heidelberg University Hospital, Heidelberg, ;Germany., Sommerer C; Department of Nephrology, Heidelberg University Hospital, Heidelberg, ;Germany.; German Center for Infection Research, German Center for Infection Research (DZIF), Thematic Translational Unit (TTU)-Infections of the Immunocompromised Host (IICH), Partner Site Heidelberg, Heidelberg, ;Germany., Hückelhoven-Krauss A; Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, ;Germany., Czock D; Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Heidelberg, ;Germany., Mehrabi A; Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, ;Germany., Schwab C; Institute of Pathology, Heidelberg University Hospital, Heidelberg, ;Germany., Waldherr R; Institute of Pathology, Heidelberg University Hospital, Heidelberg, ;Germany., Schnitzler P; Center for Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, ;Germany., Merle U; Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, ;Germany., Schwenger V; Department of Nephrology, Klinikum der Landeshauptstadt Stuttgart, Stuttgart, ;Germany., Krautter M; Department of Nephrology, Klinikum der Landeshauptstadt Stuttgart, Stuttgart, ;Germany., Kemmner S; Transplant Center, University Hospital Munich, Ludwig-Maximilians University (LMU), Munich, ;Germany., Fischereder M; Division of Nephrology, Department of Internal Medicine IV, University Hospital Munich, Ludwig-Maximilians-Universität München (LMU), Munich, ;Germany., Stangl M; Department of General, Visceral, and Transplant Surgery, University Hospital Munich, Ludwig-Maximilians-Universität München (LMU), Munich, ;Germany., Hauser IA; Medical Clinic III, Department of Nephrology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, ;Germany., Kälsch AI; Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology/Pneumology), University Medical Centre Mannheim, University of Heidelberg, Mannheim, ;Germany., Krämer BK; Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology/Pneumology), University Medical Centre Mannheim, University of Heidelberg, Mannheim, ;Germany., Böhmig GA; Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, ;Austria., Müller-Tidow C; Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, ;Germany., Reiser J; Department of Medicine, Rush University, Chicago, IL, ;United States., Zeier M; Department of Nephrology, Heidelberg University Hospital, Heidelberg, ;Germany., Schmitt M; Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, ;Germany., Terness P; Institute of Immunology, Heidelberg University Hospital, Heidelberg, ;Germany., Schmitt A; TolerogenixX GmbH, Heidelberg, ;Germany.; Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, ;Germany., Daniel V; Institute of Immunology, Heidelberg University Hospital, Heidelberg, ;Germany. |
| المصدر: | Frontiers in immunology [Front Immunol] 2023 Jul 11; Vol. 14, pp. 1089664. Date of Electronic Publication: 2023 Jul 11 (Print Publication: 2023). |
| نوع المنشور: | Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Kidney Transplantation*, Humans ; Follow-Up Studies ; Prospective Studies ; Retrospective Studies ; Antibodies ; Disease Progression |
| مستخلص: | Background: The administration of modified immune cells (MIC) before kidney transplantation led to specific immunosuppression against the allogeneic donor and a significant increase in regulatory B lymphocytes. We wondered how this approach affected the continued clinical course of these patients. Methods: Ten patients from a phase I clinical trial who had received MIC infusions prior to kidney transplantation were retrospectively compared to 15 matched standard-risk recipients. Follow-up was until year five after surgery. Results: The 10 MIC patients had an excellent clinical course with stable kidney graft function, no donor-specific human leukocyte antigen antibodies (DSA) or acute rejections, and no opportunistic infections. In comparison, a retrospectively matched control group receiving standard immunosuppressive therapy had a higher frequency of DSA (log rank P = 0.046) and more opportunistic infections (log rank P = 0.033). Importantly, MIC patients, and in particular the four patients who had received the highest cell number 7 days before surgery and received low immunosuppression during follow-up, continued to show a lack of anti-donor T lymphocyte reactivity in vitro and high CD19 + CD24 hi CD38 hi transitional and CD19 + CD24 hi CD27 + memory B lymphocytes until year five after surgery. Conclusions: MIC infusions together with reduced conventional immunosuppression were associated with good graft function during five years of follow-up, no de novo DSA development and no opportunistic infections. In the future, MIC infusions might contribute to graft protection while reducing the side effects of immunosuppressive therapy. However, this approach needs further validation in direct comparison with prospective controls. Trial Registration: https://clinicaltrials.gov/, identifier NCT02560220 (for the TOL-1 Study). EudraCT Number: 2014-002086-30. Competing Interests: MSa, CMo, CK, GO, MZ, MSm, PT, and ASm together with the University of Heidelberg, are co-founders of TolerogenixX GmbH, Heidelberg, Germany, a biotechnology company that holds licenses for MIC treatment. CK, GO, and PT hold a patent for MIC treatment. MSa, CMo, CK, GO, CSü, MZ, MSm, PT, AS, and VD together with the University of Heidelberg and TolerogenixX GmbH filed a patent application for MIC treatment. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Schaier, Morath, Wang, Kleist, Opelz, Tran, Scherer, Pham, Ekpoom, Süsal, Ponath, Kälble, Speer, Benning, Nusshag, Mahler, Pego da Silva, Sommerer, Hückelhoven-Krauss, Czock, Mehrabi, Schwab, Waldherr, Schnitzler, Merle, Schwenger, Krautter, Kemmner, Fischereder, Stangl, Hauser, Kälsch, Krämer, Böhmig, Müller-Tidow, Reiser, Zeier, Schmitt, Terness, Schmitt and Daniel.) |
| References: | Am J Transplant. 2012 May;12(5):1157-67. (PMID: 22429309) Am J Transplant. 2012 Feb;12(2):388-99. (PMID: 22081892) Nat Rev Nephrol. 2012 Apr 17;8(6):348-57. (PMID: 22508180) Am J Transplant. 2013 Aug;13(8):2096-105. (PMID: 23750878) Am J Transplant. 2015 May;15(5):1384-91. (PMID: 25808898) Front Immunol. 2022 May 26;13:874157. (PMID: 35720402) J Clin Invest. 2020 May 1;130(5):2364-2376. (PMID: 31990685) Clin Infect Dis. 2020 Oct 23;71(7):e159-e169. (PMID: 31915816) Pediatr Nephrol. 2018 Feb;33(2):199-213. (PMID: 28229281) Am J Transplant. 2019 Feb;19(2):324-330. (PMID: 30133954) Transpl Int. 2006 Jan;19(1):19-26. (PMID: 16359373) Am J Transplant. 2015 Mar;15(3):695-704. (PMID: 25693475) J Clin Invest. 2010 Jun;120(6):1848-61. (PMID: 20501943) PLoS One. 2016 Apr 05;11(4):e0153170. (PMID: 27045291) J Clin Invest. 2010 Jun;120(6):1836-47. (PMID: 20501946) Clin Sci (Lond). 2015 May;128(9):593-607. (PMID: 25495457) J Am Soc Nephrol. 2023 Jan 1;34(1):160-174. (PMID: 36137752) BMJ. 2020 Oct 21;371:m3734. (PMID: 33087345) Transplantation. 2015 Sep;99(9):1976-80. (PMID: 25769065) Open Forum Infect Dis. 2022 May 13;9(7):ofac243. (PMID: 35855001) Lancet. 2020 May 23;395(10237):1627-1639. (PMID: 32446407) N Engl J Med. 2013 Sep 26;369(13):1215-26. (PMID: 24066742) BMJ Open. 2022 Nov 11;12(11):e066128. (PMID: 36368749) Hum Immunol. 2015 Jul;76(7):480-7. (PMID: 26074415) Hum Immunol. 2018 May;79(5):272-276. (PMID: 29409743) J Clin Invest. 2017 Jun 30;127(7):2505-2512. (PMID: 28665300) Am J Transplant. 2021 Apr;21(4):1603-1611. (PMID: 33171020) J Am Soc Nephrol. 2020 Dec;31(12):2887-2899. (PMID: 32908001) J Am Soc Nephrol. 2004 Jun;15(6):1582-8. (PMID: 15153569) |
| فهرسة مساهمة: | Keywords: cell therapy; phase I (drug development); regulatory B (Breg) cells; tolerance; transplantation - kidney |
| سلسلة جزيئية: | ClinicalTrials.gov NCT02560220 |
| المشرفين على المادة: | 0 (Antibodies) |
| تواريخ الأحداث: | Date Created: 20230724 Date Completed: 20230726 Latest Revision: 20230726 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC10361653 |
| DOI: | 10.3389/fimmu.2023.1089664 |
| PMID: | 37483623 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2023.1089664 |