SEARCH:   Advanced

Blood, 15 November 2006, Vol. 108, No. 10, pp. 3313-3320. Prepublished online as a Blood First Edition Paper on July 25, 2006; DOI 10.1182/blood-2006-03-006908. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-03-006908v1 108/10/3313    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bauer, T. R. Articles by Hickstein, D. D. Search for Related Content PubMed PubMed Citation Articles by Bauer, T. R., Jr Articles by Hickstein, D. D. Related Collections Hematopoiesis and Stem Cells Phagocytes Cell Adhesion and Motility Stem Cells in Hematology Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Correction of the disease phenotype in canine leukocyte adhesion deficiency using ex vivo hematopoietic stem cell gene therapy Thomas R. Bauer, Jr, Mehreen Hai, Laura M. Tuschong, Tanya H. Burkholder, Yu-chen Gu, Robert A. Sokolic, Cole Ferguson, Cynthia E. Dunbar, and Dennis D. Hickstein From the Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH); the Division of Veterinary Resources, Office of Research Services, NIH; and the Molecular Hematopoiesis Section, Hematology Branch, National Heart, Lung, Blood Institute, NIH, Bethesda, MD. Canine leukocyte adhesion deficiency (CLAD) represents the canine counter-part of the human disease leukocyte adhesion deficiency (LAD). Defects in the leukocyte integrin CD18 adhesion molecule in both CLAD and LAD lead to recurrent, life-threatening bacterial infections. We evaluated ex vivo retroviral-mediated gene therapy in CLAD using 2 nonmyeloablative conditioning regimens—200 cGy total body irradiation (TBI) or 10 mg/kg busulfan—with or without posttransplantation immunosuppression. In 6 of 11 treated CLAD dogs, therapeutic levels of CD18+ leukocytes were achieved. Conditioning with either TBI or busulfan allowed long-term engraftment, and immunosuppression was not required for efficacy. The percentage of CD18+ leukocytes in the peripheral blood progressively increased over 6 to 8 months after infusion to levels ranging from 1.26% to 8.37% at 1-year follow-up in the 6 dogs. These levels resulted in reversal or moderation of the severe CLAD phenotype. Linear amplification–mediated polymerase chain reaction assays indicated polyclonality of insertion sites. These results describe ex vivo hematopoietic stem cell gene transfer in a disease-specific, large animal model using 2 clinically applicable conditioning regimens, and they provide support for the use of nonmyeloablative conditioning regimens in preclinical protocols of retroviral-mediated gene transfer for nonmalignant hematopoietic diseases such as LAD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020