Cholera toxin is a potent adjuvant for dendritic cell vaccination: Increased tumor-speciric CD8(+) cytotoxic activity is associated with decreased CD25+CD4+T cells

We investigated the development of CD8(+) tumor-specific cytotoxic lymphocytes (CTL) and protection against tumor growth after vaccination with bone-marrow-derived DC pulsed with a model protein antigen, ovalbumin, conjugated to cholera toxin (OVA-CT) in B6 mice using E.G7 tumor cells expressing OVA-peptide(257-264) (SIINFEKL) as target cells in vitro and in vivo. Vaccination with OVA-CT-pulsed DC concurrently induced strong CTL in vitro activity and anti-E.G7 tumor protection in vivo in WT, NK-depleted and CD4-deficient mice as well as in IL-12-/- and IFN-g-/- mice but not in CD8-deficient mice. Interestingly, increase in number of splenic CTL were found to be associated with decreased expression of CD25+CD4+ T cells in mice treated with OVA-CT-pulsed DC. These results suggest that conjugation of tumor Ag to CT for DC vaccination represents a promising approach for tumor vaccination and immunotherapy.