Abstract 2716: Development of tanapox virus for oncolytic therapy

• Published in: Cancer research (Chicago, Ill.) Ill.), 2012-04, Vol.72 (8_Supplement), p.2716-2716
• Main Authors: Seibert, Krystal N., Essani, Karim, Bejcek, Bruce E.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2012-2716

Vaccinia virus has been included in the many viruses that have been used to target cancer cells. However, vaccinia virus has some drawbacks in that it infects both tumor and non-tumor cells (Guo, Z. S. etal. 2005 Cancer Research 65: 9991-9998), and hosts often have a pre-existing immunity to it (Hu, Y. etal. 2001 J. Virol. 75, 10300-10308). Due to these drawbacks with vaccinia virus we are developing a poxvirus family member, tanapox virus (TPV), for use as an oncolytic therapy. TPV does not cross-react with vaccinia virus antibodies, replicates in human cells, and results in a relatively mild infection under normal conditions making it safer to work with (Paulose, M. etal. 1998 Microbial Pathogenesis 25, 33-41). Tumor suppressor protein p53 is mutated in over half of all cancers making it a promising target for virotherapy. In this study we characterized the 142R protein of TPV, demonstrating its potential as a conditionally replicating oncolytic virus. By analyzing the sequence of 142R it was determined that the protein has a serine-threonine kinase domain that is homologous to the vaccinia virus B1R gene that has been shown to phosphorylate p53. Viral tropism towards cancer can be enhanced by engineering the virus to be conditionally replicating (Vähä-Koskela, M. J. V. etal. 2007 Cancer Letters 254, 178-216), such as the adenovirus ONYX-015 in which the E1B gene has been deleted, restricting its replication to cells not containing a wild-type p53. When comparing the sequence of 142R to B1R we showed that 142R had 50% identity to B1R. 142R also has the same nucleotide binding, phosphotransfer and proton transfer, ATP binding and catalytic domain indicator regions as B1R. We then created a plasmid with 142R that was transfected into COS-7 cells, harvested and the protein eluted from a cobalt column. This protein was then used in a protein kinase assay against p53. This indicates that the 142R protein of TPV is capable of interacting with p53 so is a good candidate for creating a conditionally replicating virus. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2716. doi:1538-7445.AM2012-2716