Oncolytic Viruses

Adenovirus

Adenovirus can be modified to allow for viral growth within tumors in a relatively selective manner. One deletion that confers tumor selectivity is within the E1B region, found in the vector 0NYX-015, which restricts viral replication to cells lacking normal p53 function (13). Based on gene mutations alone, this vector could be of use in a majority of human glioblastomas, not only those carrying mutations in the p53 gene (14), but also in those that contain the frequent deletion in CDKN2, whose gene (p14ARF) is required for proper p53 function. Other adenoviral mutants have been constructed so they will grow within tumors that contain mutations/deletions or dysfunctions in the p16/pRB pathway. Another type of mutant will target cells expressing the EGFR or integrins, which are often upregulated in gliomas.

Reovirus

This nonenveloped RNA virus, with little pathogenicity to humans, will replicate/grow and kill selectively only in cells with an activated Ras pathway. This is a common occurrence with gliomas because of either constitutively active EGFR or platelet-derived growth factor receptor (PDGFR). When the virus is administered intravenously to animals bearing subcutaneous tumors, potent antitumor activity occurs in a variety of tumor types (15). Importantly, the virus shows excellent potency and safety profiles in animal models of gliomas. A phase I study is being planned in Canada.

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