المؤلفون: Sawitzki, Birgit, Harden, Paul N, Reinke, Petra, Moreau, Aurélie, Hutchinson, James A, Game, David S, Tang, Qizhi, Guinan, Eva C, Battaglia, Manuela, Burlingham, William J, Roberts, Ian SD, Streitz, Mathias, Josien, Régis, Böger, Carsten A, Scottà, Cristiano, Markmann, James F, Hester, Joanna L, Juerchott, Karsten, Braudeau, Cecile, James, Ben, Contreras-Ruiz, Laura, van der Net, Jeroen B, Bergler, Tobias, Caldara, Rossana, Petchey, William, Edinger, Matthias, Dupas, Nathalie, Kapinsky, Michael, Mutzbauer, Ingrid, Otto, Natalie M, Öllinger, Robert, Hernandez-Fuentes, Maria P, Issa, Fadi, Ahrens, Norbert, Meyenberg, Christoph, Karitzky, Sandra, Kunzendorf, Ulrich, Knechtle, Stuart J, Grinyó, Josep, Morris, Peter J, Brent, Leslie, Bushell, Andrew, Turka, Laurence A, Bluestone, Jeffrey A, Lechler, Robert I, Schlitt, Hans J, Cuturi, Maria C, Schlickeiser, Stephan, Friend, Peter J, Miloud, Tewfik, Scheffold, Alexander, Secchi, Antonio, Crisalli, Kerry, Kang, Sang-Mo, Hilton, Rachel, Banas, Bernhard, Blancho, Gilles, Volk, Hans-Dieter, Lombardi, Giovanna, Wood, Kathryn J, Geissler, Edward K

المصدر: Lancet (London, England). 395(10237)

مصطلحات موضوعية: Dendritic Cells, Macrophages, Humans, Immunosuppressive Agents, Kidney Transplantation, Graft Rejection, T-Lymphocytes, Regulatory, Cell- and Tissue-Based Therapy, Immunosuppression Therapy, Kidney Disease, Transplantation, Organ Transplantation, Patient Safety, Clinical Research, Clinical Trials and Supportive Activities, Renal and urogenital, Medical and Health Sciences, General & Internal Medicine

الوصف: BackgroundUse of cell-based medicinal products (CBMPs) represents a state-of-the-art approach for reducing general immunosuppression in organ transplantation. We tested multiple regulatory CBMPs in kidney transplant trials to establish the safety of regulatory CBMPs when combined with reduced immunosuppressive treatment.MethodsThe ONE Study consisted of seven investigator-led, single-arm trials done internationally at eight hospitals in France, Germany, Italy, the UK, and the USA (60 week follow-up). Included patients were living-donor kidney transplant recipients aged 18 years and older. The reference group trial (RGT) was a standard-of-care group given basiliximab, tapered steroids, mycophenolate mofetil, and tacrolimus. Six non-randomised phase 1/2A cell therapy group (CTG) trials were pooled and analysed, in which patients received one of six CBMPs containing regulatory T cells, dendritic cells, or macrophages; patient selection and immunosuppression mirrored the RGT, except basiliximab induction was substituted with CBMPs and mycophenolate mofetil tapering was allowed. None of the trials were randomised and none of the individuals involved were masked. The primary endpoint was biopsy-confirmed acute rejection (BCAR) within 60 weeks after transplantation; adverse event coding was centralised. The RTG and CTG trials are registered with ClinicalTrials.gov, NCT01656135, NCT02252055, NCT02085629, NCT02244801, NCT02371434, NCT02129881, and NCT02091232.FindingsThe seven trials took place between Dec 11, 2012, and Nov 14, 2018. Of 782 patients assessed for eligibility, 130 (17%) patients were enrolled and 104 were treated and included in the analysis. The 66 patients who were treated in the RGT were 73% male and had a median age of 47 years. The 38 patients who were treated across six CTG trials were 71% male and had a median age of 45 years. Standard-of-care immunosuppression in the recipients in the RGT resulted in a 12% BCAR rate (expected range 3·2-18·0). The overall BCAR rate for the six parallel CTG trials was 16%. 15 (40%) patients given CBMPs were successfully weaned from mycophenolate mofetil and maintained on tacrolimus monotherapy. Combined adverse event data and BCAR episodes from all six CTG trials revealed no safety concerns when compared with the RGT. Fewer episodes of infections were registered in CTG trials versus the RGT.InterpretationRegulatory cell therapy is achievable and safe in living-donor kidney transplant recipients, and is associated with fewer infectious complications, but similar rejection rates in the first year. Therefore, immune cell therapy is a potentially useful therapeutic approach in recipients of kidney transplant to minimise the burden of general immunosuppression.FundingThe 7th EU Framework Programme.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7bj1w6wkTest

المؤلفون: Sawitzki, Birgit, Harden, Paul N., Reinke, Petra, Moreau, Aurelie, Hutchinson, James A., Game, David S., Tang, Qizhi, Guinan, Eva C., Battaglia, Manuela, Burlingham, William J., Roberts, Ian S. D., Streitz, Mathias, Josien, Regis, Boeger, Carsten A., Scotta, Cristiano, Markmann, James F., Hester, Joanna L., Juerchott, Karsten, Braudeau, Cecile, James, Ben, Contreras-Ruiz, Laura, van der Net, Jeroen B., Bergler, Tobias, Caldara, Rossana, Petchey, William, Edinger, Matthias, Dupas, Nathalie, Kapinsky, Michael, Mutzbauer, Ingrid, Otto, Natalie M., Oellinger, Robert, Hernandez-Fuentes, Maria P., Issa, Fadi, Ahrens, Norbert, Meyenberg, Christoph, Karitzky, Sandra, Kunzendorf, Ulrich, Knechtle, Stuart J., Grinyo, Josep, Morris, Peter J., Brent, Leslie, Bushell, Andrew, Turka, Laurence A., Bluestone, Jeffrey A., Lechler, Robert I., Schlitt, Hans J., Schlickeiser, Stephan, Cuturi, Maria C., Friend, Peter J., Miloud, Tewfik, Scheffold, Alexander, Secchi, Antonio, Crisalli, Kerry, Kang, Sang-Mo, Hilton, Rachel, Banas, Bernhard, Blancho, Gilles, Volk, Hans-Dieter, Lombardi, Giovanna, Wood, Kathryn J., Geissler, Edward K.

مصطلحات موضوعية: 610 Medizin, ddc:610

العلاقة: Sawitzki, Birgit, Harden, Paul N., Reinke, Petra, Moreau, Aurelie, Hutchinson, James A. , Game, David S., Tang, Qizhi, Guinan, Eva C., Battaglia, Manuela, Burlingham, William J., Roberts, Ian S. D., Streitz, Mathias, Josien, Regis, Boeger, Carsten A., Scotta, Cristiano, Markmann, James F., Hester, Joanna L., Juerchott, Karsten, Braudeau, Cecile, James, Ben, Contreras-Ruiz, Laura, van der Net, Jeroen B., Bergler, Tobias, Caldara, Rossana, Petchey, William, Edinger, Matthias, Dupas, Nathalie, Kapinsky, Michael, Mutzbauer, Ingrid, Otto, Natalie M., Oellinger, Robert, Hernandez-Fuentes, Maria P., Issa, Fadi , Ahrens, Norbert , Meyenberg, Christoph, Karitzky, Sandra, Kunzendorf, Ulrich, Knechtle, Stuart J., Grinyo, Josep, Morris, Peter J., Brent, Leslie, Bushell, Andrew, Turka, Laurence A., Bluestone, Jeffrey A., Lechler, Robert I., Schlitt, Hans J. , Schlickeiser, Stephan, Cuturi, Maria C., Friend, Peter J., Miloud, Tewfik, Scheffold, Alexander , Secchi, Antonio, Crisalli, Kerry, Kang, Sang-Mo, Hilton, Rachel, Banas, Bernhard , Blancho, Gilles, Volk, Hans-Dieter, Lombardi, Giovanna, Wood, Kathryn J. und Geissler, Edward K. (2020) Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials (vol 395, pg 1627, 2020). The lancet 395 (10242), S. 1972.

الإتاحة: https://epub.uni-regensburg.de/37892Test/

المؤلفون: Beriou, Gaelle, Moreau, Aurelie, Cuturi, Maria C.

المصدر: Current Opinion in Organ Transplantation ; volume 17, issue 1, page 42-47 ; ISSN 1087-2418

الإتاحة: https://doi.org/10.1097/mot.0b013e32834ee662Test

المؤلفون: Hill, Marcelo, Cuturi, Maria C

المصدر: Current Opinion in Organ Transplantation ; volume 15, issue 6, page 738-743 ; ISSN 1087-2418

الإتاحة: https://doi.org/10.1097/mot.0b013e32833f7114Test

المؤلفون: Beriou, Gaelle, Moreau, Aurelie, Cuturi, Maria C.

المصدر: Current Opinion in Organ Transplantation; Feb2012, Vol. 17 Issue 1, p42-47, 6p