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- Title
Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals.
- Authors
Leen, Ann M; Myers, G Doug; Sili, Uluhan; Huls, M Helen; Weiss, Heidi; Leung, Kathryn S; Carrum, George; Krance, Robert A; Chang, Chung-Che; Molldrem, Jeffrey J; Gee, Adrian P; Brenner, Malcolm K; Heslop, Helen E; Rooney, Cliona M; Bollard, Catherine M
- 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.
- Publication
Nature medicine, 2006, Vol 12, Issue 10, p1160
- ISSN
1078-8956
- Publication type
Journal Article
- DOI
10.1038/nm1475