Monotherapy with the novel human anti-CD154 monoclonal antibody ABI793 in rhesus monkey renal transplantation model

Turan Kanmaz, John H. Fechner, Jose Torrealba, Hyoung Tae Kim, Yinchen Dong, Terry D. Oberley, Jacqueline M. Schultz, Debra D. Bloom, Masaaki Katayama, Wasim Dar, Judit Markovits, Walter Schuler, Huaizhong Hu, Majed M. Hamawy, Stuart J. Knechtle

Research output: Contribution to journalArticle

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Abstract

Background. This study assesses the safety and efficacy of the novel human anti-human CD154 monoclonal antibody ABI793 in rhesus monkeys. Methods. Outbred rhesus monkeys were used for renal transplantation from major histocompatibility complex-mismatched donors. Seven recipients were treated with ABI793, and six untreated recipients were used as controls. Graft function was monitored by urine output, serum creatinine, and renal biopsy. Phenotypic analysis of peripheral blood lymphocytes and mixed lymphocyte reaction were performed before transplantation and periodically after transplantation. Anti-donor major histocompatibility complex class I antibody levels were measured at the time of sacrifice. Results. Monkeys in the treated group demonstrated prolonged graft survival compared with controls. One monkey was sacrificed because of a urine leak on postoperative day 13. Three monkeys were sacrificed because of acute rejection (days 44, 149, and 158). Two monkeys were sacrificed because of chronic active rejection (days 154 and 221). One monkey was sacrificed on day 139 without rejection to observe the effects of ABI793 in the absence of rejection. There were no obvious clinical side effects of ABI793, but microscopic thromboembolic changes were observed in two monkeys. Lymphocyte subsets remained unaltered in all monkeys. Mixed lymphocyte reaction showed nonspecific suppression 6 weeks after transplantation. The monkeys with chronic active rejection showed relatively strong alloantibody responses. Conclusions. ABI793 induces prolonged renal allograft survival in rhesus monkeys. Nevertheless, thromboembolic complications may occur and chronic allograft nephropathy may develop after anti-CD154 treatment is discontinued.

Original languageEnglish (US)
Pages (from-to)914-920
Number of pages7
JournalTransplantation
Volume77
Issue number6
DOIs
StatePublished - Mar 27 2004

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Macaca mulatta
Kidney Transplantation
Haplorhini
Mixed Lymphocyte Culture Test
Transplantation
Major Histocompatibility Complex
Allografts
Urine
Kidney
Isoantibodies
ABI793 monoclonal antibody
Immunoglobulin Isotypes
Lymphocyte Subsets
Graft Survival
Creatinine
Lymphocytes
Transplants
Biopsy
Safety
Serum

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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Monotherapy with the novel human anti-CD154 monoclonal antibody ABI793 in rhesus monkey renal transplantation model. / Kanmaz, Turan; Fechner, John H.; Torrealba, Jose; Kim, Hyoung Tae; Dong, Yinchen; Oberley, Terry D.; Schultz, Jacqueline M.; Bloom, Debra D.; Katayama, Masaaki; Dar, Wasim; Markovits, Judit; Schuler, Walter; Hu, Huaizhong; Hamawy, Majed M.; Knechtle, Stuart J.

In: Transplantation, Vol. 77, No. 6, 27.03.2004, p. 914-920.

Research output: Contribution to journalArticle

Kanmaz, T, Fechner, JH, Torrealba, J, Kim, HT, Dong, Y, Oberley, TD, Schultz, JM, Bloom, DD, Katayama, M, Dar, W, Markovits, J, Schuler, W, Hu, H, Hamawy, MM & Knechtle, SJ 2004, 'Monotherapy with the novel human anti-CD154 monoclonal antibody ABI793 in rhesus monkey renal transplantation model', Transplantation, vol. 77, no. 6, pp. 914-920. https://doi.org/10.1097/01.TP.0000116392.72152.75
Kanmaz, Turan ; Fechner, John H. ; Torrealba, Jose ; Kim, Hyoung Tae ; Dong, Yinchen ; Oberley, Terry D. ; Schultz, Jacqueline M. ; Bloom, Debra D. ; Katayama, Masaaki ; Dar, Wasim ; Markovits, Judit ; Schuler, Walter ; Hu, Huaizhong ; Hamawy, Majed M. ; Knechtle, Stuart J. / Monotherapy with the novel human anti-CD154 monoclonal antibody ABI793 in rhesus monkey renal transplantation model. In: Transplantation. 2004 ; Vol. 77, No. 6. pp. 914-920.
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AU - Kanmaz, Turan

AU - Fechner, John H.

AU - Torrealba, Jose

AU - Kim, Hyoung Tae

AU - Dong, Yinchen

AU - Oberley, Terry D.

AU - Schultz, Jacqueline M.

AU - Bloom, Debra D.

AU - Katayama, Masaaki

AU - Dar, Wasim

AU - Markovits, Judit

AU - Schuler, Walter

AU - Hu, Huaizhong

AU - Hamawy, Majed M.

AU - Knechtle, Stuart J.

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N2 - Background. This study assesses the safety and efficacy of the novel human anti-human CD154 monoclonal antibody ABI793 in rhesus monkeys. Methods. Outbred rhesus monkeys were used for renal transplantation from major histocompatibility complex-mismatched donors. Seven recipients were treated with ABI793, and six untreated recipients were used as controls. Graft function was monitored by urine output, serum creatinine, and renal biopsy. Phenotypic analysis of peripheral blood lymphocytes and mixed lymphocyte reaction were performed before transplantation and periodically after transplantation. Anti-donor major histocompatibility complex class I antibody levels were measured at the time of sacrifice. Results. Monkeys in the treated group demonstrated prolonged graft survival compared with controls. One monkey was sacrificed because of a urine leak on postoperative day 13. Three monkeys were sacrificed because of acute rejection (days 44, 149, and 158). Two monkeys were sacrificed because of chronic active rejection (days 154 and 221). One monkey was sacrificed on day 139 without rejection to observe the effects of ABI793 in the absence of rejection. There were no obvious clinical side effects of ABI793, but microscopic thromboembolic changes were observed in two monkeys. Lymphocyte subsets remained unaltered in all monkeys. Mixed lymphocyte reaction showed nonspecific suppression 6 weeks after transplantation. The monkeys with chronic active rejection showed relatively strong alloantibody responses. Conclusions. ABI793 induces prolonged renal allograft survival in rhesus monkeys. Nevertheless, thromboembolic complications may occur and chronic allograft nephropathy may develop after anti-CD154 treatment is discontinued.

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