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An. R. Acad. Nac. Farm., 2010, 76 (3): 327-342

ARTÍCULO

Antitumoral activity of oncolytic vaccinia virus
expressing the interferon-induced ds-RNA
dependent protein kinase PKR

María Ángeles García1,2, Magdalena Krupa1, Mariano Esteban1

1 Departamento de Biología Molecular y Celular, Centro Nacional de Biotec-
nología, CSIC, Campus de Cantoblanco, 28049 Madrid, Spain.
2 Fundación para la Investigación Biosanitaria de Andalucía Oriental Alejan-
dro Otero, Instituto de Biopatología y Medicina Regenerativa, Centro de
Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, 18100
Armilla, Granada.
Recibido el 8 de junio de 2010.

ABSTRACT

Tumour cells generally become more susceptible to virus infec-
tion than normal cells due, in part, to a deficient interferon (IFN)-
induced antiviral pathway. One of the key IFN-induced enzymes with
potent antiviral action is the ds-RNA dependent protein kinase PKR,
that once activated blocks protein synthesis, triggers apoptosis and
prevents cell growth. Among viruses, vaccinia virus (VACV) lacking
selected viral genes or armed with cytokines or tumour specific anti-
gens has been used in preclinical and clinical studies as a therapeu-
tic agent against different tumours. Here we showed in a mouse mod-
el of aggressive cancer by subcutaneous inoculation with prostate
TRAMP-C1 cells, that a VACV recombinant expressing low levels of
human PKR (VV-PKR) and lacking thymidine kinase (TK), is capa-
ble of reducing tumour burden when administered by a systemic
route in immunocompetent C57/BL6 mice. In addition, expression of
PKR was found to attenuate the virus, thus ensuring safety. A cata-
litically inactive enzyme PKR with a point mutation (K296R) induced
similar oncolytic activity as the control virus lacking TK. These find-

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