Iscalimab Combined With Transient Tesidolumab Prolongs Survival in Pig-to-Rhesus Monkey Renal Xenografts

被引：1
作者：
Adams, Andrew B. [1 ]
Faber, David [1 ]
Lovasik, Brendan P. [2 ]
Matar, Abraham J. [1 ]
Kim, Steven C. [2 ]
Burlak, Christopher [3 ]
Tector, Matt [4 ]
Tector, Alfred J. [3 ]
机构：
[1] Univ Minnesota, Sch Med, Dept Surg, Minneapolis, MN USA
[2] Emory Univ, Sch Med, Dept Surg, Atlanta, GA USA
[3] Univ Miami, Sch Med, Dept Surg, Miami, FL 33136 USA
[4] Makana Therapeut, Miami, FL USA
来源：
XENOTRANSPLANTATION | 2024年 / 31卷 / 04期
关键词：
anti-CD40 costimulation blockade; anti-complement therapy; kidney transplantation; xenotransplantation; ANTIBODY-MEDIATED REJECTION; MONOCLONAL-ANTIBODY; ALLOGRAFT SURVIVAL; NONHUMAN-PRIMATES; PORCINE ISLETS; KIDNEY; BLOCKADE; BELATACEPT; CELLS;
D O I：
10.1111/xen.12880
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
ObjectiveTo evaluate the clinically relevant anti-CD40 antibody iscalimab for baseline immunosuppression in a preclinical pig-to-rhesus renal xenograft model.Summary Background DataCD40/CD40L co-stimulation blockade-based immunosuppression has been more successful than calcineurin-based protocols in prolonging xenograft survival in preclinical models.MethodsGGTA1 knockout/CD55 transgenic pig kidneys were transplanted into rhesus monkeys (n = 6) receiving an iscalimab-based immunosuppressive regimen.ResultsTwo grafts were lost early (22 and 26 days) because of ectatic donor ureters with otherwise normal histology. The other recipients survived 171, 315, 422, and 439 days with good renal function throughout the posttransplant course. None of the recipients experienced serious infectious morbidity.ConclusionsIt may be reasonable to evaluate an iscalimab-based immunosuppressive regimen in clinical renal xenotransplantation.
引用
收藏
页数：10
相关论文
共 49 条
  • [1] Heterologous immunity provides a potent barrier to transplantation tolerance
    Adams, AB
    Williams, MA
    Jones, TR
    Shirasugi, N
    Durham, MM
    Kaech, SM
    Wherry, EJ
    Onami, T
    Lanier, JG
    Kokko, KE
    Pearson, TC
    Ahmed, R
    Larsen, CP
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (12) : 1887 - 1895
  • [2] Anti-C5 Antibody Tesidolumab Reduces Early Antibody-mediated Rejection and Prolongs Survival in Renal Xenotransplantation
    Adams, Andrew B.
    Lovasik, Brendan P.
    Faber, David A.
    Burlak, Christopher
    Breeden, Cynthia
    Estrada, Jose L.
    Reyes, Luz M.
    Vianna, Rodrigo M.
    Tector, Matthew F.
    Tector, Alfred Joseph
    [J]. ANNALS OF SURGERY, 2021, 274 (03) : 473 - 480
  • [3] Xenoantigen Deletion and Chemical Immunosuppression Can Prolong Renal Xenograft Survival
    Adams, Andrew B.
    Kim, Steven C.
    Martens, Gregory R.
    Ladowski, Joseph M.
    Estrada, Jose L.
    Reyes, Luz M.
    Breeden, Cindy
    Stephenson, Allison
    Eckhoff, Devin E.
    Tector, Matt
    Tector, Alfred Joseph
    [J]. ANNALS OF SURGERY, 2018, 268 (04) : 564 - 573
  • [4] The anti-CD40L monoclonal antibody AT-1501 promotes islet and kidney allograft survival and function in nonhuman primates
    Anwar, Imran J.
    Berman, Dora M.
    Delaura, Isabel
    Gao, Qimeng
    Willman, Melissa A.
    Miller, Allison
    Gill, Alan
    Gill, Cindy
    Perrin, Steve
    Ricordi, Camillo
    Ruiz, Philip
    Song, Mingqing
    Ladowski, Joseph M.
    Kirk, Allan D.
    Kenyon, Norma S.
    [J]. SCIENCE TRANSLATIONAL MEDICINE, 2023, 15 (711)
  • [5] Antibody reactivity with new antigens revealed in multi-transgenic triple knockout pigs may cause early loss of pig kidneys in baboons
    Ariyoshi, Yuichi
    Takeuchi, Kazuhiro
    Pomposelli, Thomas
    Ekanayake-Alper, Dilrukshi K.
    Shimizu, Akira
    Boyd, Lennan
    Estime, Ermance
    Ohta, Mayu
    Asfour, Arsenoi
    Arn, J. Scott
    Ayares, David
    Lorber, Marc
    Sykes, Megan
    Sachs, David
    Yamada, Kazuhiko
    [J]. XENOTRANSPLANTATION, 2021, 28 (01)
  • [6] Eculizumab epitope on complement C5: Progress towards a better understanding of the mechanism of action
    Brachet, Guillaume
    Bourquard, Thomas
    Gallay, Nathalie
    Reiter, Eric
    Gouilleux-Gruart, Valerie
    Poupon, Anne
    Watier, Herve
    [J]. MOLECULAR IMMUNOLOGY, 2016, 77 : 126 - 131
  • [7] Antibody-Mediated Rejection in Sensitized Nonhuman Primates: Modeling Human Biology
    Burghuber, C. K.
    Kwun, J.
    Page, E. J.
    Manook, M.
    Gibby, A. C.
    Leopardi, F. V.
    Song, M.
    Farris, A. B., III
    Hong, J. J.
    Villinger, F.
    Adams, A. B.
    Iwakoshi, N. N.
    Knechtle, S. J.
    [J]. AMERICAN JOURNAL OF TRANSPLANTATION, 2016, 16 (06) : 1726 - 1738
  • [8] CALNE RY, 1979, LANCET, V2, P1033
  • [9] Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways
    Cardona, K
    Korbutt, GS
    Milas, Z
    Lyon, J
    Cano, J
    Jiang, W
    Bello-Laborn, H
    Hacquoil, B
    Strobert, E
    Gangappa, S
    Weber, CJ
    Pearson, TC
    Rajotte, RV
    Larsen, CP
    [J]. NATURE MEDICINE, 2006, 12 (03) : 304 - 306
  • [10] A Novel, Blocking, Fc-Silent Anti-CD40 Monoclonal Antibody Prolongs Nonhuman Primate Renal Allograft Survival in the Absence of B Cell Depletion
    Cordoba, F.
    Wieczorek, G.
    Audet, M.
    Roth, L.
    Schneider, M. A.
    Kunkler, A.
    Stuber, N.
    Erard, M.
    Ceci, M.
    Baumgartner, R.
    Apolloni, R.
    Cattini, A.
    Robert, G.
    Ristig, D.
    Munz, J.
    Haeberli, L.
    Grau, R.
    Sickert, D.
    Heusser, C.
    Espie, P.
    Bruns, C.
    Patel, D.
    Rush, J. S.
    [J]. AMERICAN JOURNAL OF TRANSPLANTATION, 2015, 15 (11) : 2825 - 2836
12345