title: Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals.
abstract: Immunocompromised individuals are at high risk for life-threatening diseases, especially those caused by cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus. Conventional therapeutics are primarily active only against CMV, and resistance is frequent. Adoptive transfer of polyclonal cytotoxic T lymphocytes (CTLs) specific for CMV or EBV seems promising, but it is unclear whether this strategy can be extended to adenovirus, which comprises many serotypes. In addition, the preparation of a specific CTL line for each virus in every eligible individual would be impractical. Here we describe genetic modification of antigen-presenting cell lines to facilitate the production of CD4(+) and CD8(+) T lymphocytes specific for CMV, EBV and several serotypes of adenovirus from a single cell culture. When administered to immunocompromised individuals, the single T lymphocyte line expands into multiple discrete virus-specific populations that supply clinically measurable antiviral activity. Monoculture-derived multispecific CTL infusion could provide a safe and efficient means to restore virus-specific immunity in the immunocompromised host.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, Texas 77030, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Leen
authors.forename: G Doug
authors.initials: GD
authors.lastname: Myers
authors.forename: Uluhan
authors.initials: U
authors.lastname: Sili
authors.forename: M Helen
authors.initials: MH
authors.lastname: Huls
authors.forename: Heidi
authors.initials: H
authors.lastname: Weiss
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Leung
authors.forename: George
authors.initials: G
authors.lastname: Carrum
authors.forename: Robert A
authors.initials: RA
authors.lastname: Krance
authors.forename: Chung-Che
authors.initials: CC
authors.lastname: Chang
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Molldrem
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Gee
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Brenner
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
authors.forename: Cliona M
authors.initials: CM
authors.lastname: Rooney
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000821:virology; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000378:metabolism; D005260:Female; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D007154:Immune System Diseases / Q000097:blood* / Q000628:therapy*; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism