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

• Edus H. Warren

  Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;

• Nobuharu Fujii

  Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;

• Yoshiki Akatsuka

  Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan;

• Colette N. Chaney

  Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;

• Jeffrey K. Mito

  Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;

• Keith R. Loeb

  Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;

• Ted A. Gooley

  Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;

• Michele L. Brown

  Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;

• Kevin K. W. Koo

  Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;

• Kellie V. Rosinski

  Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;

• Seishi Ogawa

  Cell Therapy and Transplantation Medicine, Cancer Genomics Project, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; and

• Aiko Matsubara

  Cell Therapy and Transplantation Medicine, Cancer Genomics Project, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; and

• Frederick R. Appelbaum

  Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;

• Stanley R. Riddell

  Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;

抄録

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.

収録刊行物

• Blood

  Blood 115 (19), 3869-3878, 2010-05-13

  American Society of Hematology

キーワード

• Cell Biology
• Hematology
• Immunology
• Biochemistry

詳細情報

• CRID: 1360846643884642048
• NII論文ID: 20001514282
• DOI: 10.1182/blood-2009-10-248997
• ISSN: 15280020
• ISSN: 00064971
• Web Site: http://ashpublications.org/blood/article-pdf/115/19/3869/1324206/zh801910003869.pdf
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