Disease relevance of Oncolytic Viruses

• Using replication-competent HSV-1 oncolytic viruses with thymidine kinase (TK) under control of different promoters, we demonstrate that viral infection, proliferation and promoter characteristics all interact to influence FIAU accumulation and imaging [1].
• This new oncolytic virus (MGH2) displays increased antitumor efficacy against human glioma cells both in vitro and in vivo when combined with cyclophosphamide and CPT-11 [2].
• CONCLUSIONS: These results suggest that oncolytic virus therapy with G47Delta can be usefully combined with androgen ablation therapy for the treatment of prostate cancer [3].
• CONCLUSIONS: The telomerase-targeted adenovirus vector has significant potential as an oncolytic virus as well as a tumor-specific therapeutic gene delivery vehicle [4].

High impact information on Oncolytic Viruses

• Unlike our previous findings with less potent oncolytic viruses, though, the preadministration of cyclophosphamide did not enhance this survival or affect oncolytic virus tumor distribution and tumor volume [5].
• Based on these results the DeltaE1B or ONYX-015 virus has been proposed to be an oncolytic virus which might be useful to treat p53-deficient tumors [6].
• At the level of transduction that can be achieved currently with oncolytic viruses given intravenously, drugs such as RAD001, which do not require activation by the virus, produce greater increases in efficacy than prodrugs such as CB1954 [7].
• We suggest that the SCGB2A2 promoter/enhancer should be particularly advantageous for gene therapy protocols involving oncolytic viruses or toxic gene transfer via adenovectors to mammary tumors [8].
• The data suggest mechanisms for disruption of nucleolar function common to oncogenic or oncolytic virus lytic growth and cell transformation [9].

Chemical compound and disease context of Oncolytic Viruses

• Cyclophosphamide allows for in vivo dose reduction of a potent oncolytic virus [5].
• CONCLUSION: Cisplatin-induced GADD34 expression selectively enhanced the cytotoxicity of the gamma(1)34.5-deficient oncolytic virus, NV1066 [10].
• To reduce the virulence of the oncolytic viruses, we inactivated them either with heat (56 degrees C/45 min) or with formalin [11].

Anatomical context of Oncolytic Viruses

• We have investigated this hypothesis by analyzing the apoptotic effects of various oncolytic viruses on the human colon carcinoma HCT116 cells and their derivatives lacking either p53 or bax gene [12].

Gene context of Oncolytic Viruses

• These studies demonstrate that an oncolytic virus driven by the telomerase promoter can be used to effectively kill a wide variety of cancer cell types and has the potential to treat primary and metastatic cancer of diverse origins [13].
• Molecular therapeutic strategies to normalize p53 signaling in cells with mutant p53 include pharmacologic rescue of mutant protein, gene therapy approaches, small-molecule agonists of downstream inhibitory genes, antisense approaches and oncolytic viruses [14].
• These results indicate that M protein mutant viruses are superior candidates as oncolytic viruses for therapies of prostate tumors, but future strategies for use of VSV will require testing individual tumors for their susceptibility to virus infection [15].
• Several strategies may be employed to achieve the tumor-selective gene delivery that is required for the success of P450 GDEPT; these include the use of tumor-targeted cellular vectors and tumor-selective oncolytic viruses [16].
• An international meeting was held on the development and application of replicating viruses for cancer therapy this past March in Banff, Alberta. In this review, using the presentations at this meeting as a backdrop, we discuss how recent scientific and clinical findings are reshaping the development of oncolytic virus therapeutics [17].

Analytical, diagnostic and therapeutic context of Oncolytic Viruses

• These findings thus show that cyclophosphamide allows for dose reduction of doses of a relatively potent oncolytic virus, a finding with implications for the development of clinical trials [5].

References