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. 2011 Jul 26;19(10):1802–1812. doi: 10.1038/mt.2011.147

Figure 5.

Figure 5

Careful scheduling of paclitaxel chemotherapy and oncolytic virotherapy leads to significant tumor therapy. (a) C57BL/6 mice (7/8 per group) seeded 7 days previously with B16-VEGF tumors were treated intraperitoneally with an injection of either phosphate-buffered saline (PBS) (PBS-Reo) or paclitaxel (Pac-PBS; Pac-Reo) for three consecutive days followed by intravenous injections of either reovirus (PBS-Reo; Pac-Reo) or PBS (Pac-PBS) for the following two consecutive days. A fourth group received two daily injections of Reovirus followed by three daily injections of paclitaxel (Reo-Pac). This cycle of five injections, with 2 days rest, was repeated three times, so that the whole treatment schedule was completed in 3 weeks. Survival with time (tumors reaching a diameter of >1.0 cm in any diameter) is shown. Results are representative of three different experiments. (b) Correlation of in vivo transduction of B16 tumors by systemically delivered reovirus with paclitaxel treatment. C57BL/6 mice bearing 14 day established B16 tumors were given daily injections of paclitaxel followed 24 hours, 48 hours or 72 hours later by a single intravenous injection of reovirus. Alternatively tumor-bearing mice were treated with reovirus and paclitaxel on the same days, with just reovirus or with no virus. Forty-eight hours following the injection of virus, tumors were excised and prepared for immunohistochemistry. Data shown are the mean number of viral infected cells/1 cm area (n = 3) and the s.d. of the mean. *Mean number of viral infected cancer cells per 1 cm area; **Standard deviation of the mean. Representative results from two mice per group (n = 3–5) are shown. (c–h) In separate experiments, C57BL/6 mice bearing 14 day established B16 tumors were given daily injections of PBS followed 24 hours later by a single injection of (c) reovirus or (d) PBS; or mice were given daily injections of paclitaxel followed (e) 24 hours, (f) 48 hours, or (g) 72 hours later by a single intravenous injection of reovirus. (h) B16 tumors from mice treated with daily injections of paclitaxel and reovirus. Forty-eight hours following the injection of virus, tumors were excised and prepared for immunohistochemistry. Virally infected cells are brown while negative tumor cells are blue. Cancer cells infected with reovirus were very commonly found around necrotic/degenerated cancer cells.