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Five-year follow-up of a phase I trial of donor-derived modified immune cell infusion in kidney transplantation

Authors :
Matthias Schaier
Christian Morath
Lei Wang
Christian Kleist
Gerhard Opelz
Thuong Hien Tran
Sabine Scherer
Lien Pham
Naruemol Ekpoom
Caner Süsal
Gerald Ponath
Florian Kälble
Claudius Speer
Louise Benning
Christian Nusshag
Christoph F. Mahler
Luiza Pego da Silva
Claudia Sommerer
Angela Hückelhoven-Krauss
David Czock
Arianeb Mehrabi
Constantin Schwab
Rüdiger Waldherr
Paul Schnitzler
Uta Merle
Vedat Schwenger
Markus Krautter
Stephan Kemmner
Michael Fischereder
Manfred Stangl
Ingeborg A. Hauser
Anna-Isabelle Kälsch
Bernhard K. Krämer
Georg A. Böhmig
Carsten Müller-Tidow
Jochen Reiser
Martin Zeier
Michael Schmitt
Peter Terness
Anita Schmitt
Volker Daniel
Source :
Frontiers in Immunology, Vol 14 (2023)
Publication Year :
2023
Publisher :
Frontiers Media S.A., 2023.

Abstract

BackgroundThe 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.MethodsTen 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.ResultsThe 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+CD24hiCD38hi transitional and CD19+CD24hiCD27+ memory B lymphocytes until year five after surgery.ConclusionsMIC 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 registrationhttps://clinicaltrials.gov/, identifier NCT02560220 (for the TOL-1 Study). EudraCT Number: 2014-002086-30.

Details

Language :
English
ISSN :
16643224
Volume :
14
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.8a3a583d0ee42d7b2d399e91afea0aa
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2023.1089664