Figure 6
Doxycycline enhances in vivo effects of oncolytic vaccinia therapy alone, or in combination with CIK cell-mediated viral delivery. (a) Mice (athymic nu-/nu- bearing subcutaneous MDA-MB 231 tumors of 50–100 mm3) were treated with oncolytic vaccinia strain WR.TK- expressing luciferase (1 × 107 PFU delivered via tail vein) with or without doxycycline (n=7 per group). Subsequent viral gene expression was determined by bioluminescence imaging at the indicated times for a region of interest over the tumor (top) or the torso (bottom) of the mice (*P<0.05). (b) Therapeutic effect of the same treatments with tumor volume determined by caliper measurement (*P<0.05). (c) Mice as before (athymic nu-/nu- with MDA MB 231 tumors) were treated with PBS, doxycycline, hCIK (1 × 107) pre-mixed with vvDD (1 × 107 PFU); or CIK/vvDD and doxycycline (n=10 per group). CIK cells were labeled with cy5.5 prior to injection and fluorescence from within the tumor was determined after 72 h by whole animal fluorescence imaging (*P=0.027). (d) Bioluminescence imaging t the same time point determined viral gene expression from within the tumor (*P=0.0009). (e) Caliper measurements followed subsequent effect on tumor volume. Doxycycline alone had no effect on tumor growth, whereas CIK/vvDD showed significant benefit relative to control from day 60, and CIK/vvDD plus doxycycline was significantly better than any other treatment from day 44 onwards (P<0.5). At the end of the experiment 2 of 8 mice in the CIK-vvDD group displayed complete responses and 6 of 8 in the CIK/vvDD plus doxycycline group.
