Monitoring the Efficacy of Oncolytic Viruses via Gene Expression

Abstract

With the recent success of oncolytic viruses in clinical trials, efforts toward improved monitoring of the viruses and their mechanism have intensified. Four main gene expression strategies have been employed to date including: analyzing overall gene expression in tumor cells, looking at gene expression of a few specific genes in the tumor cells, focusing on gene expression of specific transgenes introduced into the virus, and following gene expression of certain viral genes. Each strategy presents certain advantages and disadvantages over the others. Various methods to organize the dysregulated genes into clusters have provided a window into the mechanism of action for these viruses. Methodologically, the combined approach of looking at both overall gene expression, the tumor cells and gene expression of viral genes, enables researchers to assess correlation between the introduction of the virus and the changes in the tumor. This would seem to be the most productive approach for future studies, providing much information on mechanism and timing.

Preclinical safety evaluation of hepatic arterial infusion of oncolytic poxvirus

“…In vitro and in vivo markers that are commonly used for monitoring OVs include the following: 1) overall tumor genes’ expression, 2) specific genes’ expression in tumor cells, and 3) transgenes introduced into the viral genes. 22 And the recently developed fourth class of markers are viral genes, such as A56 that was used in this study. A56 is expressed exclusively on the membrane of cells that are infected by poxvirus, 23 and because oncolytic poxvirus VV tk− was designed to selectively infect cancer cells, in our study, A56 was only detected in tumor tissues but not in other non-tumor tissues after HAI administration of high doses of VV tk− , suggesting that HAI is a safe route of administration with regards to organ accumulation and toxicity.…”

Oncolytic virotherapy in cancer treatment: challenges and optimization prospects

“…Some potential biomarkers to assess the pharmacodynamic activity of OVs are also under way, which include assessing specific gene expression in cancer or assessing specific viral gene expression ( 97 )(29164063). Cathepsins B and L are useful biomarkers for the efficacy of reovirus-mediated tumor cell killing ( 98 ), and serum high-mobility group box 1 (HMGB1) protein was reported to be a potential predictive and prognostic biomarker for adenoviruses combined with immunotherapy ( 99 ).…”

Evolving Role of Oncolytic Virotherapy: Challenges and Prospects in Clinical Practice

“…Delivery of the OVs can be quantified by various PCR assays on the viral genome or expression analysis of viral proteins or engineered transgenes. 96 Highthroughput expression analysis of custom-designed immune-associated pathways has been used to assess the immunomodulatory impact of OVs, and several biomarkers have been proposed to be predictive of efficacy with different OVs. [97][98][99] Different signaling pathways have been studied to identify markers associated with treatment response, but the clinical translation of these biomarkers is still under investigation.…”

“…Identification of innate immune system activation and recruitment (quantitative analysis of TIL, natural killer cells, and DCs, etc) and expression analysis of IFN-γ, progressive disease-L1, granzyme B, and functional analysis of CD8 phenotype have been used to quantify alterations in TME. 2,96 Biomarkers are an essential component of oncolytic virotherapy and they will continue to evolve as our knowledge of the molecular landscape of tumor-OV interaction continues to expand.…”