Combination immunotherapy targeting angiogenesis-associated products and tumor antigens. Mice were immunized twice weekly with 3 × 105 DCs for each antigen for a combined 6 × 105 DCs per mouse. (A) B16/F10.9 melanoma model as described in Figure 3A. Syngeneic tumor RNA (B16) was used as source of tumor antigens and actin mRNA was used as control antigen. Relative to the control group (PBS), P values were less than .05 for all groups except actin (P = .4206). The overall significance of the study as determined by the Kruskal-Wallis test was P = .001. (B) MBT-2 bladder tumor model as described in Figure 3B. Syngeneic tumor RNA (MBT-2) and TERT mRNA were used as source of tumor antigens and actin mRNA as control antigen. Day-18 measurements are shown. Relative to the control group (PBS), P values were less than .05 for all groups except actin (P=.13). The overall significance of the study as determined by the Kruskal-Wallis test was P<.0001. (C) Time to appearance of palpable tumors in the experiment shown in panel B. The log-rank test (Mantel-Haenszel test) was used to determine the differences between individual groups. Relative to the combination group (MBT-2 + VEGFR-2), P values were .02 and .001 for groups immunized with MBT-2 + actin and VEGFR-2 + actin, respectively. The median time to tumor onset for MBT-2 + actin was 20 days, VEGFR-2 + actin was 15 days, and MBT-2 + VEGFR-2 was 40 days.
