Journal: Cancer research
Article Title: Radiation-Induced Enhancement of Antitumor T-cell Immunity by VEGF-Targeted 4–1BB Costimulation
doi: 10.1158/0008-5472.CAN-16-2105
Figure Lengend Snippet: Inhibition of irradiated and nonirradiated tumors in mice treated with PD-1 antibody, CTLA-4 antibody, and VEGF-4–1BB aptamer conjugates. 4T1 tumor cells were implanted subcutaneously in the right and left flanks of Balb/c mice at days 0 and 8, respectively. At day 13 when the tumors in the right flank reached an average size of 75 mm3, they were irradiated once with 12 Gy, and 3 days later treated as shown three times 2 days apart. Tumor volume at day 19 postirradiation is shown for the irradiated tumor, right flank (RF; A) and for nonirradiated tumor, left flank (LF; seven or eight mice per group; B). Time course of tumor growth is shown in Supplementary Fig. S4. Statistical analysis: A, differences between untreated group and groups treated by radiation, CTLA-4 antibody, PD-1 antibody, CTLA-4 + PD-1 antibody, or VEGF-4–1BB conjugate were significant (P < 0.05), whereas no significant differences were seen among the treated groups. Combination with radiation was significant for all treatments, PD-1, P = 0.0075; CTLA-4, P = 0.0191; PD-1 + CTLA-4, P = 0.0164; VEGF-4–1BB, P = 0.0071. B, Differences between untreated or radiated group and groups treated with CTLA-4 antibody, PD-1 antibody, CTLA-4 + PD-1 antibody, and VEGF-4–1BB conjugate were significant (P < 0.05). Differences between groups treated with radiation and PD-1 antibody or with PD-1 + CTLA-4 antibody and groups treated with antibody alone was not significant. Differences were significant between CTLA-4 antibody versus radiation + CTLA-4 antibody, P = 0.0265, and VEGF-4–1BB aptamer conjugate and radiation + VEGF-4–1BB aptamer conjugate groups, P = 0.0412. C, Survival of mice treated as described above. Mice were sacrificed when either tumor reached 1,000 mm3. Difference between untreated group and either radiation, PD-1 antibody, radiation + PD-1 antibody, CTLA-4 antibody, and VEGF-4–1BB aptamer conjugate-treated groups showed a trend but did not reach statistical significance. Differences between radiation + CTLA-4 antibody, PD-1 + CTLA-4 antibodies with or without radiation, and radiation + VEGF-4–1BB aptamer conjugate-treated groups and rest of the treatment groups was significant. Differences between radiation + VEGF-4–1BB aptamer conjugates or with PD-1 + CTLA-4 antibodies groups and PD-1 + CTLA-4 antibodies or radiation + CTLA-4 antibody-treated groups exhibited a trend but did not reach statistical significance.
Article Snippet: Nonspecific immunoreactivity in slide-mounted tissue sections was blocked with Serum-Blocking Reagent D (R&D Systems), and incubated with goat polyclonal anti-mouse VEGF at 1:20 (R&D Systems) at 4°C overnight, washed with PBS, and incubated with biotinylated anti-goat secondary antibody (R&D Systems) for 40 minutes, followed by high-sensitivity streptavidin (HSS)-horseradish peroxidase (HRP; R&D Systems) for 30 minutes.
Techniques: Inhibition, Irradiation