PMID- 35694562
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2468-0249 (Electronic)
IS  - 2468-0249 (Linking)
VI  - 7
IP  - 6
DP  - 2022 Jun
TI  - Study Design: Human Leukocyte Antigen Class I Molecule A( *)02-Chimeric Antigen 
      Receptor Regulatory T Cells in Renal Transplantation.
PG  - 1258-1267
LID - 10.1016/j.ekir.2022.03.030 [doi]
AB  - INTRODUCTION: Cell therapy with regulatory T cells (Tregs) in solid organ 
      transplantation is a promising approach for the prevention of graft rejection and 
      induction of immunologic tolerance. Previous clinical studies have demonstrated 
      the safety of Tregs in renal transplant recipients. Antigen-specific Tregs, such 
      as chimeric antigen receptor (CAR)-Tregs, are expected to be more efficacious 
      than polyclonal Tregs in homing to the target antigen. We have developed an 
      autologous cell therapy (TX200-TR101) where a human leukocyte antigen (HLA) class 
      I molecule A( *)02 (HLA-A( *)02)-CAR is introduced into autologous naive Tregs from 
      a patient with HLA-A( *)02-negative end-stage renal disease (ESRD) awaiting an 
      HLA-A( *)02-positive donor kidney. METHODS: This article describes the design of 
      the STEADFAST study, a first-in-human, phase I/IIa, multicenter, open-label, 
      single-ascending dose, dose-ranging study to assess TX200-TR101 in living-donor 
      renal transplant recipients. Up to 15 transplant recipients will receive 
      TX200-TR101 and will be followed up for a total of 84 weeks post-transplant, 
      alongside a control cohort of up to 6 transplant recipients. All transplant 
      recipients will receive a standard of care immunosuppressive regimen, with the 
      intent of intensified tapering of the regimen in the TX200-TR101 cohort. RESULTS: 
      The primary end point is the incidence and severity of treatment-emergent adverse 
      events (AEs) within 28 days post-TX200-TR101 infusion. Other end points include 
      additional safety parameters, clinical and renal outcome parameters, and the 
      evaluation of biomarkers. CONCLUSION: The STEADFAST study represents the next 
      frontier in adoptive cell therapies. TX200-TR101 holds great potential to prevent 
      immune-mediated graft rejection and induce immunologic tolerance after 
      HLA-A( *)02-mismatched renal transplantation.
CI  - (c) 2022 International Society of Nephrology. Published by Elsevier Inc.
FAU - Schreeb, Katharina
AU  - Schreeb K
AD  - Sangamo Therapeutics France, Valbonne, France.
FAU - Culme-Seymour, Emily
AU  - Culme-Seymour E
AD  - Sangamo Therapeutics France, Valbonne, France.
FAU - Ridha, Essra
AU  - Ridha E
AD  - Sangamo Therapeutics France, Valbonne, France.
FAU - Dumont, Celine
AU  - Dumont C
AD  - Sangamo Therapeutics France, Valbonne, France.
FAU - Atkinson, Gillian
AU  - Atkinson G
AD  - Sangamo Therapeutics France, Valbonne, France.
FAU - Hsu, Ben
AU  - Hsu B
AD  - Sangamo Therapeutics France, Valbonne, France.
FAU - Reinke, Petra
AU  - Reinke P
AD  - Berlin Center for Advanced Therapies (BeCAT), Berlin Institute of Health (BIH) 
      Center for Regenerative Therapies (BCRT), Charite Universitaetsmedizin Berlin, 
      Berlin, Germany.
LA  - eng
PT  - Journal Article
DEP - 20220406
PL  - United States
TA  - Kidney Int Rep
JT  - Kidney international reports
JID - 101684752
PMC - PMC9174048
OTO - NOTNLM
OT  - CAR-Tregs
OT  - HLA-A *02 mismatch
OT  - acute and chronic kidney rejection
OT  - end-stage renal disease
OT  - immunotherapy
OT  - living-donor kidney transplantation
EDAT- 2022/06/14 06:00
MHDA- 2022/06/14 06:01
PMCR- 2022/04/06
CRDT- 2022/06/13 03:34
PHST- 2021/12/09 00:00 [received]
PHST- 2022/03/04 00:00 [revised]
PHST- 2022/03/28 00:00 [accepted]
PHST- 2022/06/13 03:34 [entrez]
PHST- 2022/06/14 06:00 [pubmed]
PHST- 2022/06/14 06:01 [medline]
PHST- 2022/04/06 00:00 [pmc-release]
AID - S2468-0249(22)01250-5 [pii]
AID - 10.1016/j.ekir.2022.03.030 [doi]
PST - epublish
SO  - Kidney Int Rep. 2022 Apr 6;7(6):1258-1267. doi: 10.1016/j.ekir.2022.03.030. 
      eCollection 2022 Jun.