Nature Medicine
- 12, 1160 - 1166 (2006)
Published online: 24 September 2006; | doi:10.1038/nm1475
Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individualsAnn M Leen1, 2, 8, G Doug Myers1, 2, 8, Uluhan Sili1, M Helen Huls1, Heidi Weiss4, Kathryn S Leung1, 2, George Carrum1, 4, Robert A Krance1, 2, 4, Chung-Che Chang6, Jeffrey J Molldrem7, Adrian P Gee1, 2, 4, Malcolm K Brenner1, 2, 4, Helen E Heslop1, 2, 4, Cliona M Rooney1, 2, 3, 5 & Catherine M Bollard1, 2, 3, 41
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, Texas 77030, USA. 2
Department of Pediatrics, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, Texas 77030, USA. 3
Department of Immunology, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, Texas 77030, USA. 4
Department of Medicine, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, Texas 77030, USA. 5
Department of Virology, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, Texas 77030, USA. 6
Department of Pathology, Weill Medical College of Cornell University, TMHRI, The Methodist Hospital, Houston, Texas 77030, USA. 7
Department of Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. 8
These authors contributed equally to this work.
Correspondence should be addressed to Catherine M Bollard cmbollar@txccc.org 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.
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