Home Neoplasma 2003 Neoplasma Vol.50, p.296-299, 2003

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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

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Neoplasma Vol.50, p.296-299, 2003

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

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, RFT5-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.

Year: 2003, Volume: 50, Issue: Page From: 296, Page To: 299

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