FIGURE 6.
Prophylactic and therapeutic antitumor efficacy following a single immunization with ID-VP02. A, BALB/c mice (5 per group) were immunized with indicated doses, in vector genomes, of ID-VP02 encoding AH1A5, a heteroclitic mutant of the endogenous CT26 tumor rejection epitope AH1, linked to OVA (OVA-AH1A5) or HBSS vehicle alone. At day 12 postimmunization, the percentage of AH1A5-specific or AH1-specific splenic CD8 T cells was measured by ICS. *P≤0.05 and between indicated groups (Mann-Whitney). B, Twelve days after immunization, a 1:1:1 mixture of dye-labeled target cells each pulsed with AH1, AH1A5, or a control peptide were transferred intravenously into immunized and naive mice (3 per group). The following day, spleens were harvested and the relative recovery of each population was compared between naive and immunized mice to calculate specific killing. *P≤0.05 and **P≤0.01 compared with naive (Mann-Whitney). C and D, BALB/c mice (10 per group) were injected subcutaneously with 8×104 CT26 tumor cells on the right flank and mice were euthanized when tumors exceeded 100 mm2. Mice were either left untreated, treated prophylactically 28 days before challenge with 4×109 vector genomes of ID-VP02 encoding OVA-AH1A5, or treated therapeutically 4 days postchallenge with the same dose of vector. Survival curves are shown in (C) and individual tumor growth curves are shown in (D). **P≤0.01 and ***P≤0.001 compared with untreated (Mantel-Cox).