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

AM Leen, GD Myers, U Sili, MH Huls, H Weiss… - Nature medicine, 2006 - nature.com
AM Leen, GD Myers, U Sili, MH Huls, H Weiss, KS Leung, G Carrum, RA Krance, CC Chang…
Nature medicine, 2006nature.com
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 …
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.
nature.com