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

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

Research output: Contribution to journalArticle

432 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1160-1166
Number of pages7
JournalNature Medicine
Volume12
Issue number10
DOIs
StatePublished - Oct 2006

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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