Author: ["Ann M Leen","G Doug Myers","Uluhan Sili","M Helen Huls","Heidi Weiss","Kathryn S Leung","George Carrum","Robert A Krance","Chung-Che Chang","Jeffrey J Molldrem","Adrian P Gee","Malcolm K Brenner","Helen E Heslop","Cliona M Rooney","Catherine M Bollard"]
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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.Cite this article
Leen, A., Myers, G., Sili, U. et al. Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals. Nat Med 12, 1160–1166 (2006). https://doi.org/10.1038/nm1475 