title: Production of good manufacturing practice-grade cytotoxic T lymphocytes specific for Epstein-Barr virus, cytomegalovirus and adenovirus to prevent or treat viral infections post-allogeneic hematopoietic stem cell transplant.
abstract: Infections with a range of common community viruses remain a major cause of mortality and morbidity after allogeneic hematopoietic stem cell transplantation. T cells specific for cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenoviruses can safely prevent and infections with these three most common culprits, but the manufacture of individual T cell lines for each virus would be prohibitive in terms of time and cost. We have demonstrated that T cells specific for all three viruses can be manufactured in a single culture using monocytes and EBV-transformed B lymphoblastoid cell lines (LCLs), both transduced with an adenovirus vector expressing pp65 of CMV, as antigen-presenting cells. Trivirus-specific T cell lines produced from healthy stem cell donors could prevent and treat infections with all three viruses, not only in the designated recipient, but in unrelated, partially-HLA-matched third party recipients. We now provide the details and logistics of T cell manufacture.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, The Methodist Hospital, Houston, Texas 77030, USA.
authors.forename: Uluhan
authors.initials: U
authors.lastname: Sili
authors.forename: Ann M
authors.initials: AM
authors.lastname: Leen
authors.forename: Juan F
authors.initials: JF
authors.lastname: Vera
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Gee
authors.forename: Helen
authors.initials: H
authors.lastname: Huls
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
authors.forename: Cliona M
authors.initials: CM
authors.lastname: Rooney
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000637:transplantation; D018929:Cell Culture Techniques; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D010750:Phosphoproteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation; D014184:Transplantation, Homologous / Q000009:adverse effects; D014763:Viral Matrix Proteins / Q000276:immunology; D014777:Virus Diseases / Q000209:etiology* / Q000628:therapy
chemical_list: D006680:HLA Antigens; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa