Donor antigen-specific regulatory T cell administration to recipients of live donor kidneys : A ONE Study consortium pilot trial
Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved..
Regulatory T cells (Tregs) can inhibit cellular immunity in diverse experimental models and have entered early phase clinical trials in autoimmunity and transplantation to assess safety and efficacy. As part of the ONE Study consortium, we conducted a phase I-II clinical trial in which purified donor antigen reactive (dar)-Tregs (CD4+CD25+CD127lo) were administered to 3 patients, 7 to 11 days after live donor renal transplant. Recipients received a modified immunosuppression regimen, without induction therapy, consisting of maintenance tacrolimus, mycophenolate mofetil, and steroids. Steroids were weaned off over 14 weeks. No rejection was seen on any protocol biopsy. Therefore, all patients discontinued mycophenolate mofetil 11 to 13 months posttransplant, per protocol. An early for-cause biopsy in 1 patient, 5 days after dar-Treg infusion, revealed absence of rejection and accumulation of Tregs in the kidney allograft. All patients had Treg-containing lymphoid aggregates evident on protocol biopsies performed 8 months posttransplant. The patients are now all >6 years posttransplant on tacrolimus monotherapy with excellent graft function. None experienced rejection episodes. No serious adverse events were attributable to Treg administration. These results support a favorable safety profile of dar-Tregs administered early after renal transplant, suggest early biopsy might be an instructive research endpoint and provide preliminary evidence of potential immunomodulatory activity.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
|---|---|
| Enthalten in: |
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons - 23(2023), 12 vom: 07. Dez., Seite 1872-1881 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Guinan, Eva C [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Costimulation blockade |
|---|
| Anmerkungen: |
Date Completed 04.12.2023 Date Revised 04.12.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.ajt.2023.06.012 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM359231624 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM359231624 | ||
| 003 | DE-627 | ||
| 005 | 20231226080432.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ajt.2023.06.012 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1197.xml |
| 035 | |a (DE-627)NLM359231624 | ||
| 035 | |a (NLM)37422112 | ||
| 035 | |a (PII)S1600-6135(23)00543-9 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Guinan, Eva C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Donor antigen-specific regulatory T cell administration to recipients of live donor kidneys |b A ONE Study consortium pilot trial |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.12.2023 | ||
| 500 | |a Date Revised 04.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Regulatory T cells (Tregs) can inhibit cellular immunity in diverse experimental models and have entered early phase clinical trials in autoimmunity and transplantation to assess safety and efficacy. As part of the ONE Study consortium, we conducted a phase I-II clinical trial in which purified donor antigen reactive (dar)-Tregs (CD4+CD25+CD127lo) were administered to 3 patients, 7 to 11 days after live donor renal transplant. Recipients received a modified immunosuppression regimen, without induction therapy, consisting of maintenance tacrolimus, mycophenolate mofetil, and steroids. Steroids were weaned off over 14 weeks. No rejection was seen on any protocol biopsy. Therefore, all patients discontinued mycophenolate mofetil 11 to 13 months posttransplant, per protocol. An early for-cause biopsy in 1 patient, 5 days after dar-Treg infusion, revealed absence of rejection and accumulation of Tregs in the kidney allograft. All patients had Treg-containing lymphoid aggregates evident on protocol biopsies performed 8 months posttransplant. The patients are now all >6 years posttransplant on tacrolimus monotherapy with excellent graft function. None experienced rejection episodes. No serious adverse events were attributable to Treg administration. These results support a favorable safety profile of dar-Tregs administered early after renal transplant, suggest early biopsy might be an instructive research endpoint and provide preliminary evidence of potential immunomodulatory activity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Tregs | |
| 650 | 4 | |a costimulation blockade | |
| 650 | 4 | |a regulatory T cells | |
| 650 | 4 | |a renal transplantation | |
| 650 | 4 | |a safety | |
| 650 | 4 | |a transplantation tolerance | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a Tacrolimus |2 NLM | |
| 650 | 7 | |a WM0HAQ4WNM |2 NLM | |
| 650 | 7 | |a Mycophenolic Acid |2 NLM | |
| 650 | 7 | |a HU9DX48N0T |2 NLM | |
| 650 | 7 | |a Steroids |2 NLM | |
| 700 | 1 | |a Contreras-Ruiz, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Crisalli, Kerry |e verfasserin |4 aut | |
| 700 | 1 | |a Rickert, Charles |e verfasserin |4 aut | |
| 700 | 1 | |a Rosales, Ivy |e verfasserin |4 aut | |
| 700 | 1 | |a Makar, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Colvin, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Geissler, Edward K |e verfasserin |4 aut | |
| 700 | 1 | |a Sawitzki, Birgit |e verfasserin |4 aut | |
| 700 | 1 | |a Harden, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Qizhi |e verfasserin |4 aut | |
| 700 | 1 | |a Blancho, Giles |e verfasserin |4 aut | |
| 700 | 1 | |a Turka, Laurence A |e verfasserin |4 aut | |
| 700 | 1 | |a Markmann, James F |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons |d 2001 |g 23(2023), 12 vom: 07. Dez., Seite 1872-1881 |w (DE-627)NLM119667924 |x 1600-6143 |7 nnns |
| 773 | 1 | 8 | |g volume:23 |g year:2023 |g number:12 |g day:07 |g month:12 |g pages:1872-1881 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ajt.2023.06.012 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 23 |j 2023 |e 12 |b 07 |c 12 |h 1872-1881 | ||