EXTENSIVE CROSS-REACTIVITY OF ADENOVIRUS-SPECIFIC CYTOTOXIC T-CELLS

Although adenovirus is a major source of morbidity for immunocompromis ed individuals and a popular vector for gene therapy, little is known about the cellular immune responses it evokes in humans. Initial trial s using adenovirus vectors have been disappointing, probably owing bot h to a preexisting immune response to Ad2 and Ad5, the most commonly u sed vector backbones, and to a response to the transgene, The former p roblem might be overcome by switching from the common type C adenoviru ses, of which Ad2 and Ad5 are members, to other less common serotypes, Evidence for the feasibility of this approach has been provided by a rat model system. However, its success in humans depends on there bein g no immunological cross-reactivity between groups at the humoral or c ellular level. Here, we examine the cross-reactivity of the cellular i mmune response to adenovirus in a human system, and find that human cy totoxic T lymphocytes (CTLs) prepared in vitro against an adenovirus f rom two of the six subgroups can lyse cells infected with adenoviruses from the other subgroups. Hence, the proposed use of adenovirus vecto rs from uncommon subgroups to evade memory immune response to subgroup C adenoviruses may not be successful. However, this same cross-reacti vity indicates that adoptive transfer of CTLs generated in vitro again st one adenovirus serotype may protect immunocompromised patients from infections by adenoviruses of all serotypes.