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VOL. 76 (3), 327-342, 2010 ANTITUMORAL ACTIVITY OF ONCOLYTIC VACCINIA VIRUS...

Figure 4. Diminished TRAMP-C1 tumour growth in C57/BL6 mice treated with
recombinant vaccinia viruses VV-PKR, VV-K296R and VVLUC. A. Male mice
C57/BL6 seven weeks old, 10 per group, were injected by subcutaneous route with
1x107 of TRAMP-C1 mouse prostate cancer cells. At the median tumour volume of
75 to 100 mm3 (30 days post-inoculation), mice were injected by intraperitoneal route
with 5x107 pfu of vaccinia virus VVPKR, VVLUC, VVK296R, or saline PBS on days
0 and 3. Tumours were measured every 3-4 days using digital caliper. B. Virus titers
in transplantable tumours. Shown are the mean virus titers in pfu/gr of tumour tis-
sue obtained by surgery 5 days after the second dose of virus was administered by
i.p. route.

4. DISCUSSION

Oncolytic vaccinia viruses have demonstrated tumour specificity,
high levels of transgene expression, and anti-tumour effect (13-15).
PKR is an interferon-induced kinase that is able to induce apoptosis
through eIF2a and NFkB modulation, and have a discussed tumour
suppressor activity. PKR is also involved in the pathways of several tu-
mour suppressors such as p53, IRF1, ARF and MDA7 (6). To define
the contribution of PKR as an oncolytic agent, we have evaluated the
antitumoral activity of a recombinant vaccinia virus expressing PKR
inserted in the TK locus, in immunocompetent C57/BL6 mice bearing
subcutaneous tumours produced by the prostate cancer cell line

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