Evaluation of a CD25-specific immunotoxin for prevention of graft-versus-host disease after unrelated marrow transplantation

Paul J. Martin, Ji Pei, Ted Gooley, Claudio Anasetti, Frederick R. Appelbaum, Joachim Deeg, John A. Hansen, Richard A. Nash, Effie W. Petersdorf, Rainer Storb, Victor Ghetie, John Schindler, Ellen S. Vitetta

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Donor T cells activated by recipient alloantigens cause graft-versus-host disease (GVHD) after hematopoietic cell transplantation. Activated T cells express CD25, among other components of the interleukin-2 receptor. We conducted a phase I/II study to determine whether administration of CD25-specific antibody conjugated to ricin toxin A could reduce the risk of grade III or IV GVHD after marrow transplantation from HLA-matched unrelated donors. All patients received methotrexate and cyclosporine after the transplantation. The immunotoxin was given to 36 patients for 4 consecutive days beginning approximately 36 hours after the marrow infusion was completed. Fourteen (40%) of the 35 patients who could be evaluated developed grade III or IV GVHD. In a contemporaneous population of 121 patients who received marrow from HLA-matched unrelated donors and were given methotrexate and cyclosporine without the immunotoxin, the incidence of grades III and IV GVHD was 24%. Cyclosporine blocked the induction of CD25 expression on alloactivated T cells in vitro but had no detectable effect on CD25 expression by T-regulatory cells. Taken together, these results are consistent with the hypothesis that cyclosporine protected alloactivated donor T cells from the effects of the immunotoxin, whereas the CD25+ T-regulatory cells remained susceptible, causing an unexpected exacerbation of acute GVHD.

Original languageEnglish (US)
Pages (from-to)552-560
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume10
Issue number8
DOIs
Publication statusPublished - Aug 2004

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Keywords

  • CD25
  • Graft-versus-host disease
  • Hematopoietic cell transplantation
  • T-regulatory cells

ASJC Scopus subject areas

  • Transplantation

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