title: Cytomegalovirus-specific cytotoxic T lymphocytes can be efficiently expanded from granulocyte colony-stimulating factor-mobilized hemopoietic progenitor cell products ex vivo and safely transferred to stem cell transplantation recipients to facilitate immune reconstitution.
abstract: Uncontrolled cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation causes significant morbidity and mortality. Adoptive transfer of CMV-specific cytotoxic T lymphocytes (CTLs) is a promising therapy to treat reactivation and prevent viral disease. In this article, we describe the generation of clinical-grade CMV-specific CTLs directly from granulocyte colony-stimulating factor-mobilized hemopoietic progenitor cell (G-HPC) products collected for transplantation. This method requires less than 2.5% of a typical G-HPC product to reproducibly expand CMV-specific CTLs ex vivo. Comparison of 11 CMV CTL lines generated from G-HPC products with 52 CMV CTL lines generated from nonmobilized peripheral blood revealed similar expansion kinetics and phenotype. G-HPC-derived CTLs produced IFN-γ after reexposure to CMVpp65 antigen and exhibited CMV-directed cytotoxicity but no alloreactivity against transplantation recipient-derived cells. Seven patients received CMV-specific CTL lines expanded from G-HPC products in a prophylactic adoptive immunotherapy phase I/II clinical trial. Use of G-HPC products will facilitate integration of CTL generation into established quality systems of transplantation centers and more rapid inclusion of T cell therapies into routine clinical care.
authors: Westmead Millennium Institute, Westmead Institute for Cancer Research, University of Sydney, Westmead, Australia. leighton.clancy@sydney.edu.au
authors: Leighton E
authors: LE
authors: Clancy
authors: Emily
authors: E
authors: Blyth
authors: Renee M
authors: RM
authors: Simms
authors: Kenneth P
authors: KP
authors: Micklethwaite
authors: Chun-Kei K
authors: CK
authors: Ma
authors: Jane S
authors: JS
authors: Burgess
authors: Vicki
authors: V
authors: Antonenas
authors: Peter J
authors: PJ
authors: Shaw
authors: David J
authors: DJ
authors: Gottlieb
mesh_terms: D000328:Adult; D000368:Aged; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000821:virology
chemical_list: D016179:Granulocyte Colony-Stimulating Factor