Clinical-scale selective depletion of alloreactive T cells using an anti-CD25 immunotoxin

Research output: Contribution to journalArticle

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Abstract

Allogeneic hematopoietic stem cell transplantation is the treatment of choice for many hematological malignancies. Its efficacy is limited by graft-versus-host disease (GVHD), the leading cause of post-transplant morbidity and mortality. GVHD is mediated by a subpopulation of T cells in the stem cell graft. Ex vivo T cell depletion of all T cells of the graft can prevent development of GVHD but can lead to a delay in immune reconstitution and an increase of potentially lethal opportunistic infections and leukemic relapses. Hypothetically, an approach that enables a selective depletion of the alloreactive donor T cells that cause GVHD while preserving third party (anti-leukemic and anti-microbial) reactivity would be optimal for recipients of HSCT. Our preliminary data demonstrated that an anti-CD25 immunotoxin, which reacts with a cell surface activation antigen, can selectively deplete alloreactive donor T cells activated by non-leukemic recipient white blood cells while preserving the beneficial third-party reactivity in vitro. In this report we describe a method for clinical-scale ex vivo selective depletion of alloreactive donor T cells using the anti-CD25 immunotoxin, RFr5-SMPT-dgRTA. Two logs of alloreactive T cells could be selectively depleted while preserving third party reactivity. This method was reproducible in 10 pre-clinical experiments with 8 HLA-mismatched healthy volunteer pairs and 2 HLA-matched sibling donor/patient pairs.

Original languageEnglish (US)
Pages (from-to)296-299
Number of pages4
JournalNeoplasma
Volume50
Issue number4
StatePublished - 2003

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Immunotoxins
T-Lymphocytes
Graft vs Host Disease
Tissue Donors
Transplants
Hematopoietic Stem Cell Transplantation
Opportunistic Infections
Hematologic Neoplasms
Surface Antigens
Siblings
Healthy Volunteers
Leukocytes
Stem Cells
Morbidity
Recurrence
Mortality

Keywords

  • Allogeneic hematopoietic stem cell transplantation
  • Graft-versus-host disease
  • Immunotoxin
  • T cell

ASJC Scopus subject areas

  • Cancer Research

Cite this

Clinical-scale selective depletion of alloreactive T cells using an anti-CD25 immunotoxin. / Michálek, J.; Collins, R. H.; Vitetta, E. S.

In: Neoplasma, Vol. 50, No. 4, 2003, p. 296-299.

Research output: Contribution to journalArticle

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