VIRUS-MEDIATED DELIVERY OF ANTIGENIC EPITOPES INTO DENDRITIC CELLS ASA MEANS TO INDUCE CTL

Dendritic cells (DC) are potent inducers of CD8(+) T cells and can sti mulate protective antitumor immunity when pulsed with an antigenic pep tide or protein, We used a replication-deficient adenovirus containing a Kh-restricted antigenic peptide of chicken OVA to study CTL inducti on in vitro and in vivo after adenovirus-mediated gene transfer into D C, The efficiency of adenovirus-infected DC in eliciting a specific CT L response was compared with immunizations with a recombinant vaccinia virus and DC pulsed with peptide or protein, An immortalized DC line derived from a C57BL/6 mouse and freshly isolated splenic DC from C57B L/6 mice were used in CTL induction, Virus-infected DC elicited the st rongest Ag-specific CTL response in vitro and in vivo and induced prot ective antitumor immunity to a challenge with EC,7 tumors (EL-4 cell l ine expressing OVA), Direct immunization of mice with recombinant aden ovirus resulted in the induction of high titers of neutralizing Abs, w hich precluded a boost of a CTL response after repeated inoculations, However, repeated injections of virus-infected DC induced only low tit ers of neutralizing Abs. Furthermore, the presence of neutralizing Abs specific for the virus did not affect the usefulness of infected DC a s repeated applications of virus-infected DC boosted the CTL response even in mice previously infected with the recombinant vector, The use of DC infected with a recombinant virus has advantages over other form s of immunization and could provide an alternative approach for design ing vaccination therapies.