2025-07-21 ウィスコンシン大学マディソン校(UW-Madison)
<関連情報>
- https://news.wisc.edu/a-new-kidney-free-of-daily-meds/
- https://www.sciencedirect.com/science/article/abs/pii/S1600613525000735
- https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2023.11279/full
生体関連ヒト白血球抗原適合腎移植における免疫寛容の誘導: 第3相ランダム化臨床試験 Induction of immune tolerance in living related human leukocyte antigen–matched kidney transplantation: A phase 3 randomized clinical trial
Dixon B. Kaufman, Sanjeev K. Akkina, Mark.D. Stegall, James B. Piper, A. Osama Gaber, William S. Asch, Stephan Busque, Erik Stites, Michael De Vera, Titte R. Srinivas, Diane Alonso, Ashesh Shah, Anup Patel, Martin L. Mai, Kenneth D. Chavin, Meelie DebRoy, Arksarapuk Jittirat , Nadiesda Costa, Matthew Cooper, Gayle Vranic …Daniel C. Brennan,on behalf of the MDR-101-MLK Study Group
American Journal of Transplantation Available online: 6 February 2025
DOI:https://doi.org/10.1016/j.ajt.2025.01.044
Abstract
This phase 3 multicenter, randomized, controlled clinical trial evaluated investigational cellular product (MDR-101) to produce immune tolerance vs standard of care, in kidney transplant recipients. Adult recipients of kidneys from 2-haplotype human leukocyte antigen–matched living siblings were randomized 2:1 to treatment (n = 20) or control (n = 10). The MDR-101 product was from the same kidney donor. Treatment recipients received a nonmyeloablative conditioning protocol with rabbit-antithymocyte globulin and low-dose total lymphoid irradiation (10 fractions). MDR-101 was infused (day 11). Steroids were withdrawn by day 10 and mycophenolate by day 39. Tacrolimus was continued until day 180 and tapered to withdrawal 1-year posttransplant if donor hematopoietic mixed chimerism was ≥5%. Controls received immunosuppression (IS) per institutional standard of care. Twenty recipients received the MDR-101 infusion, and none developed graft versus host disease. Nineteen (95%) successfully discontinued all IS approximately 1 year after kidney transplant. Fifteen (75%) reached the primary study endpoint of IS-free for >2 years. Four resumed IS: 1 with recurrent immunoglobulin A nephropathy; 1 with recurrent immunoglobulin A nephropathy and rejection; 1 with rejection; and 1 with borderline biopsy changes. Kidney transplant recipients receiving MDR-101 achieved donor mixed chimerism and functional immune tolerance for greater than 2 years with no death, graft loss, DSA, or graft versus host disease and demonstrated improved quality of life compared to standard treatment.
アカゲザルの腎移植寛容に対するヘリカルトモセラピー全リンパ照射と造血細胞移植 Helical TomoTherapy Total Lymphoid Irradiation and Hematopoietic Cell Transplantation for Kidney Transplant Tolerance in Rhesus Macaques
Dixon B. Kaufman,Lisa J. Forrest,John Fechner,Jennifer Post,†Jennifer Coonen,Lynn D. Haynes,W. John Haynes,Neil Christensen,Weixiong Zhong,Christopher J. Little,Anthony D’Alessandro,Luis Fernandez,Kevin Brunner,Kent Jensen,William J. Burlingham,Peiman Hematti,Samuel Strober
Transplant International Published:22 June 2023
DOI:https://doi.org/10.3389/ti.2023.11279
Development of a post-transplant kidney transplant tolerance induction protocol involving a novel total lymphoid irradiation (TLI) conditioning method in a rhesus macaque model is described. We examined the feasibility of acheiving tolerance to MHC 1-haplotype matched kidney transplants by establishing a mixed chimeric state with infusion of donor hematopoietic cells (HC) using TomoTherapy TLI. The chimeric state was hypothesized to permit the elimination of all immunosuppressive (IS) medications while preserving allograft function long-term without development of graft-versus-host-disease (GVHD) or rejection. An experimental group of 11 renal transplant recipients received the tolerance induction protocol and outcomes were compared to a control group (n = 7) that received the same conditioning but without donor HC infusion. Development of mixed chimerism and operational tolerance was accomplished in two recipients in the experimental group. Both recipients were withdrawn from all IS and continued to maintain normal renal allograft function for 4 years without rejection or GVHD. None of the animals in the control group achieved tolerance when IS was eliminated. This novel experimental model demonstrated the feasibility for inducing of long-term operational tolerance when mixed chimerism is achieved using a TLI post-transplant conditioning protocol in 1-haplotype matched non-human primate recipients of combined kidney and HC transplantation.
