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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 individuals

Ann 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 Bollard1,2,3,4

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.