Research Article: Intravenously Administered Alphavirus Vector VA7 Eradicates Orthotopic Human Glioma Xenografts in Nude Mice

Date Published: January 6, 2010

Publisher: Public Library of Science

Author(s): Jari E. Heikkilä, Markus J. V. Vähä-Koskela, Janne J. Ruotsalainen, Miika W. Martikainen, Marianne M. Stanford, J. Andrea McCart, John C. Bell, Ari E. Hinkkanen, Torbjorn Ramqvist.

Abstract: VA7 is a neurotropic alphavirus vector based on an attenuated strain of Semliki Forest virus. We have previously shown that VA7 exhibits oncolytic activity against human melanoma xenografts in immunodeficient mice. The purpose of this study was to determine if intravenously administered VA7 would be effective against human glioma.

Partial Text: During the past decades malignant gliomas have presented with an insurmountable obstacle in cancer treatment. While recent results of a multi-center phase III clinical trial combining radiotherapy (RT) with the DNA-alkylating agent temozolomide (TMZ) have marked a true paradigm shift in treatment of glioblastoma multiforme (GBM) [1], the most common type of malignant glioma, patients rarely live beyond two years after diagnosis and there are no cures. Radical surgery can alleviate the effects of excess tumor burden and prolong meaningful life-span, but remains palliative only [2].

In the present paper we describe the oncolytic potential of the SFV vector VA7 in a nude mouse model of human glioma. The initial results that small subcutaneous tumors were completely eradicated by a single injection of VA7-EGFP were promising, but regrowth after initial regression of larger tumors was suggestive of emerging resistance, as seen in a human melanoma model [32]. However, as the isolated explant cultures could be killed by VA7-EGFP, mechanisms other than resistance to VA7 are responsible for the failure to achieve complete eradication of large tumors.



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