Therapy of murine tumors with recombinant Bordetella pertussis adenylate cyclase carrying a cytotoxic T cell epitope

Bordetella pertussis secretes an invasive adenylate cyclase toxin, CyaA, th at is able to deliver its N-terminal catalytic domain into the cytosol of e ukaryotic target cells directly through the cytoplasmic membrane. We have s hown previously that recombinant CyaA can be used to deliver viral CD8(+) T cell epitopes to the MHC-class I presentation pathway to trigger specific CTL responses in vivo, In the present study, we show that mice immunized wi th a detoxified but still invasive CyaA carrying a CD8(+) T cell epitope of OVA developed strong epitope-specific CTL responses, which kill tumor cell s expressing this Ag, Treating mice with this recombinant molecule after th e graft of melanoma cells expressing OVA induced a strong survival advantag e compared with control animals. To our knowledge, this study represents th e first demonstration that a nonreplicative and nontoxic vector carrying a single CTL epitope can stimulate efficient protective and therapeutic antit umor immunity.