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., and Bollard, Catherine M.
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. [ABSTRACT FROM AUTHOR]