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Initial experience with the human anti-human CD154 monoclonal antibody, ABI793, in pig-to-baboon xenotransplantation.
Knosalla, C; Ryan, D J J; Moran, K; Gollackner, B; Schuler, W; Sachs, D H; Awwad, M; Schuurman, H-J; Cooper, D K C.
Afiliação
  • Knosalla C; Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.
Xenotransplantation ; 11(4): 353-60, 2004 Jul.
Article em En | MEDLINE | ID: mdl-15196130
ABSTRACT

BACKGROUND:

ABI793 (ABI) is a human monoclonal antibody (mAb) specific for human CD154. To assess the suitability of ABI for baboon transplantation studies, we carried out in vitro studies to determine ABI's reactivity with baboon cells expressing CD154, performed in vivo pharmacokinetic studies in two baboons, and tested the effect of ABI administration on elicited antibody production in two baboons undergoing either pig hematopoietic progenitor cell (PBPC) or heterotopic heart transplantation.

METHODS:

In vitro Baboon peripheral blood mononuclear cells were activated in vitro to upregulate CD154, and binding of ABI to CD154 was measured by flow cytometry. In vivo Serum levels of ABI were measured immediately before and 15 min after the intravenous administration of ABI (20 mg/kg) to two baboons over 28 days. Subsequently, ABI (25 mg/kg on days 0, 1, 4 and 7, and then 20 mg/kg every 5 days) was included in the immunosuppressive regimen in two pig-to-baboon transplants (PBPC or heart transplantation).

RESULTS:

In vitro ABI was almost non-reactive to baboon T cells before stimulation, but bound to activated T cells. In vivo In the pharmacokinetic study, trough levels of ABI (before the next dose) ranged between 190 and 580 microg/ml, and the estimated half-life was 10-15 days. There was no apparent toxicity. Following pig PBPC or heart transplantation, no elicited antibody was detected while ABI was being administered or during several weeks of follow-up.

CONCLUSIONS:

ABI functions in baboons, is well-tolerated, and prevents an elicited antibody response to pig antigens.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Papio / Suínos / Transplante Heterólogo / Transplante de Coração / Ligante de CD40 / Anticorpos Monoclonais Limite: Animals / Humans Idioma: En Revista: Xenotransplantation Assunto da revista: TRANSPLANTE Ano de publicação: 2004 Tipo de documento: Article País de afiliação: Estados Unidos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Papio / Suínos / Transplante Heterólogo / Transplante de Coração / Ligante de CD40 / Anticorpos Monoclonais Limite: Animals / Humans Idioma: En Revista: Xenotransplantation Assunto da revista: TRANSPLANTE Ano de publicação: 2004 Tipo de documento: Article País de afiliação: Estados Unidos