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Blood. 2010 May 13;115(19):3869-78. doi: 10.1182/blood-2009-10-248997. Epub 2010 Jan 13.

Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens.

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1
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. ehwarren@u.washington.edu

Abstract

The adoptive transfer of donor T cells that recognize recipient minor histocompatibility antigens (mHAgs) is a potential strategy for preventing or treating leukemic relapse after allogeneic hematopoietic cell transplantation (HCT). A total of 7 patients with recurrent leukemia after major histocompatibility complex (MHC)-matched allogeneic HCT were treated with infusions of donor-derived, ex vivo-expanded CD8(+) cytotoxic T lymphocyte (CTL) clones specific for tissue-restricted recipient mHAgs. The safety of T-cell therapy, in vivo persistence of transferred CTLs, and disease response were assessed. Molecular characterization of the mHAgs recognized by CTL clones administered to 3 patients was performed to provide insight into the antileukemic activity and safety of T-cell therapy. Pulmonary toxicity of CTL infusion was seen in 3 patients, was severe in 1 patient, and correlated with the level of expression of the mHAg-encoding genes in lung tissue. Adoptively transferred CTLs persisted in the blood up to 21 days after infusion, and 5 patients achieved complete but transient remissions after therapy. The results of these studies illustrate the potential to selectively enhance graft-versus-leukemia activity by the adoptive transfer of mHAg-specific T-cell clones and the challenges for the broad application of this approach in allogeneic HCT. This study has been registered at http://clinicaltrials.gov as NCT00107354.

PMID:
20071660
PMCID:
PMC2869557
DOI:
10.1182/blood-2009-10-248997
[Indexed for MEDLINE]
Free PMC Article
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