{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:35:50Z","timestamp":1761100550892,"version":"3.30.1"},"reference-count":48,"publisher":"American Society of Hematology","issue":"12","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Genetically modified donor T cells with an inducible \u201csuicide\u201d gene have the potential to improve the safety and availability of allogeneic hematopoietic stem cell transplantation by enhancing engraftment and permitting control of graft-versus-host disease (GVHD). However, several clinical studies of gene-modified T cells have shown limited to no in vivo function of the ex vivo expanded T cells. Using the well-established dog model of allogeneic marrow transplantation, the question was asked if retrovirally transduced, donor derived, ex vivo expanded cytotoxic T lymphocytes (CTLs) that are recipient specific could enhance engraftment of dog leukocyte antigen (DLA)\u2013haploidentical marrow following a single dose of 9.2 Gy total body irradiation and no postgrafting immunosuppression. In this setting, only 4 of 11 control recipients of DLA-haploidentical marrow without added CTLs engrafted. CTLs did not enhance engraftment of CD34+ selected peripheral blood stem cells. However, recipient-specific CTLs enhanced engraftment of DLA-haploidentical marrow in 9 of 11 evaluable recipients (P\u2009=\u2009.049). All dogs that engrafted developed multiorgan GVHD. To facilitate in vivo tracking, 8 dogs received CTLs transduced with a retroviral vector encoding green fluorescent protein (GFP) and neomycin phosphotransferase (neo). Recipients that engrafted had sharp increases in the numbers of circulating GFP+ CTLs on days +5 to +6 after transplantation. GFP+ CTLs isolated from blood were capable of recipient-specific lysis. At necropsy, up to 7.1% of CD3+ cells in tissues were GFP+ and polymerase chain reaction in situ hybridization for neoshowed infiltration of transduced CTLs in GVHD-affected organs. These results show that ex vivo expanded, transduced T cells maintained in vivo function and enhanced marrow engraftment.<\/jats:p>","DOI":"10.1182\/blood.v98.12.3447","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:40Z","timestamp":1027774000000},"page":"3447-3455","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":11,"title":["Engraftment of DLA-haploidentical marrow with ex vivo expanded, retrovirally transduced cytotoxic T lymphocytes"],"prefix":"10.1182","volume":"98","author":[{"given":"George E.","family":"Georges","sequence":"first","affiliation":[{"name":"From the Clinical Research Division, Fred Hutchinson Cancer Research Center; Departments of Medicine and Laboratory Medicine, University of Washington, Seattle; Department of Veterinary Pathology, University of California, Davis; and Genetic Therapy, a Novartis company, Gaithersburg, MD."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer","family":"Storb","sequence":"additional","affiliation":[{"name":"From the Clinical Research Division, Fred Hutchinson Cancer Research Center; Departments of Medicine and Laboratory Medicine, University of Washington, Seattle; Department of Veterinary Pathology, University of California, Davis; and Genetic Therapy, a Novartis company, Gaithersburg, MD."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedetto","family":"Bruno","sequence":"additional","affiliation":[{"name":"From the Clinical Research Division, Fred Hutchinson Cancer Research Center; Departments of Medicine and Laboratory Medicine, University of Washington, Seattle; Department of Veterinary Pathology, University of California, Davis; and Genetic Therapy, a Novartis company, Gaithersburg, MD."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott J.","family":"Brodie","sequence":"additional","affiliation":[{"name":"From the Clinical Research Division, Fred Hutchinson Cancer Research Center; Departments of Medicine and Laboratory Medicine, University of Washington, Seattle; Department of Veterinary Pathology, University of California, Davis; and Genetic Therapy, a Novartis company, Gaithersburg, MD."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer D.","family":"Thompson","sequence":"additional","affiliation":[{"name":"From the Clinical Research Division, Fred Hutchinson Cancer Research Center; Departments of Medicine and Laboratory Medicine, University of Washington, Seattle; Department of Veterinary Pathology, University of California, Davis; and Genetic Therapy, a Novartis company, Gaithersburg, MD."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna G.","family":"Taranova","sequence":"additional","affiliation":[{"name":"From the Clinical Research Division, Fred Hutchinson Cancer Research Center; Departments of Medicine and Laboratory Medicine, University of Washington, Seattle; Department of Veterinary Pathology, University of California, Davis; and Genetic Therapy, a Novartis company, Gaithersburg, MD."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Maciej","family":"Zaucha","sequence":"additional","affiliation":[{"name":"From the Clinical Research Division, Fred Hutchinson Cancer Research Center; Departments of Medicine and Laboratory Medicine, University of Washington, Seattle; Department of Veterinary Pathology, University of California, Davis; and Genetic Therapy, a Novartis company, Gaithersburg, MD."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Te\u0301re\u0300se","family":"Little","sequence":"additional","affiliation":[{"name":"From the Clinical Research Division, Fred Hutchinson Cancer Research Center; Departments of Medicine and Laboratory Medicine, University of Washington, Seattle; Department of Veterinary Pathology, University of California, Davis; and Genetic Therapy, a Novartis company, Gaithersburg, MD."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eustacia","family":"Zellmer","sequence":"additional","affiliation":[{"name":"From the Clinical Research Division, Fred Hutchinson Cancer Research Center; Departments of Medicine and Laboratory Medicine, University of Washington, Seattle; Department of Veterinary Pathology, University of California, Davis; and Genetic Therapy, a Novartis company, Gaithersburg, MD."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter F.","family":"Moore","sequence":"additional","affiliation":[{"name":"From the Clinical Research Division, Fred Hutchinson Cancer Research Center; Departments of Medicine and Laboratory Medicine, University of Washington, Seattle; Department of Veterinary Pathology, University of California, Davis; and Genetic Therapy, a Novartis company, Gaithersburg, MD."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodore","family":"Gooley","sequence":"additional","affiliation":[{"name":"From the Clinical Research Division, Fred Hutchinson Cancer Research Center; Departments of Medicine and Laboratory Medicine, University of Washington, Seattle; Department of 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