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Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals.

Research paper by Ann M AM Leen, G Doug GD Myers, Uluhan U Sili, M Helen MH Huls, Heidi H Weiss, Kathryn S KS Leung, George G Carrum, Robert A RA Krance, Chung-Che CC Chang, Jeffrey J JJ Molldrem, Adrian P AP Gee, Malcolm K MK Brenner, Helen E HE Heslop, Cliona M CM Rooney, Catherine M CM Bollard

Indexed on: 26 Sep '06Published on: 26 Sep '06Published in: Nature Medicine



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.

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