CUTTING EDGE - PASSIVE BUT NOT ACTIVE CD8-CELL-BASED IMMUNOTHERAPY INTERFERES WITH LIVER-TUMOR PROGRESSION IN A TRANSGENIC MOUSE MODEL( T)

To evaluate tumor immunotherapies, we used transgenic mice that harbor a progressive liver tumor associated with the expression of the SV40 large tumor T oncoprotein (SV40-T), To induce ''self'' tumor Ag-specif ic CD8(+) T cells, mice were injected with an immunodominant SV40-T CT L epitope mixed with a heterologous helper peptide. Despite repeated i njections, this vaccine failed to raise a tumor-specific CD8(+) T cell response that was efficient enough to counteract tumors. Although coi mmunization with SV40-T CTL epitope and heterologous helper peptide ef ficiently recruited the respective Th cells, only low-avidity SV40-T-s pecific CD8(+) T cells were activated, Furthermore, major alterations in SV40-T-specific B and Th cell responses were characterized. In cont rast, transfers of higher-avidity CTLs specific for the same SV40-T ep itope were effective in counteracting tumors, These results suggest th at passive therapies targeted to self tumor Ag may be more suitable th an active immunization in the treatment of spontaneous tumors.