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Updated: Aug 23, 2026
Production and Purification of Non Replicative Canine Adenovirus Type 2 Derived Vectors
Published on: December 3, 2013
A conditionally replicating adenovirus for nasopharyngeal carcinoma gene therapy
Marie C Chia1, Wei Shi, Jian-Hua Li
1Division of Experimental Therapeutics, Princess Margaret Hospital/Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada M5G 2M9.
Abstract:
Successful attainment of tumor-specific gene expression was achieved in nasopharyngeal carcinoma (NPC) by exploiting the exclusive presence of the Epstein-Barr virus (EBV) genome in the cancer cells. In the current study, we have utilized an EBV-dependent transcriptional targeting strategy to construct a novel conditionally replicating adenovirus, adv.oriP.E1A. After treatment with adv.oriP.E1A, we observed extensive cell death in the EBV-positive NPC cell line C666-1. In contrast, no cytotoxicity was observed in a panel of other human EBV-negative cell lines, including fibroblasts from the nasopharynx. In vitro adenoviral replication was confirmed by the time-dependent increase in the expression of adenoviral capsid fiber protein and adenoviral DNA after C666-1 cells were infected with adv.oriP.E1A. Tumor formation was inhibited for more than 100 days after ex vivo infection of C666-1 cells with adv.oriP.E1A. Combination of local tumor radiation and adv.oriP.E1A caused complete disappearance of established tumors for at least 2 weeks in two distinct EBV-positive NPC xenograft models. Safety of this treatment was determined through the systemic delivery of adv.oriP.E1A in vivo, whereby minimal temporary perturbation of liver function was observed. We have successfully established a conditionally replicating adenovirus for EBV-positive NPC, which is both safe and efficacious, indicating a strategy that may be therapeutically applicable.
Insights
A novel adenovirus targets Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) cells, causing tumor cell death and inhibiting growth. This EBV-dependent therapy shows promise as a safe and effective treatment for NPC.
Area of Science:
- Oncolytic virology
- Gene therapy
- Cancer research
Background:
- Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV) infection.
- Targeting tumor-specific elements like the EBV genome is a strategy for cancer therapy.
- Developing targeted oncolytic viruses requires exploiting unique tumor characteristics.
Purpose of the Study:
- To construct and evaluate a novel conditionally replicating adenovirus, adv.oriP.E1A, for targeting EBV-positive NPC.
- To assess the efficacy and safety of adv.oriP.E1A in preclinical models of NPC.
- To investigate the potential of EBV-dependent gene expression for cancer treatment.
Main Methods:
- Construction of a novel adenovirus (adv.oriP.E1A) utilizing EBV-dependent replication.
- In vitro assessment of adv.oriP.E1A cytotoxicity in EBV-positive NPC cells versus EBV-negative cell lines.
- In vitro confirmation of adenoviral replication in infected NPC cells.
- Evaluation of tumor inhibition after ex vivo infection of NPC cells.
- Assessment of combination therapy with radiation in NPC xenograft models.
- In vivo safety evaluation through systemic delivery in animal models.
Main Results:
- adv.oriP.E1A demonstrated extensive cell death in EBV-positive NPC cells (C666-1) but not in EBV-negative cells.
- Adenoviral replication was confirmed in vitro by increased viral protein and DNA levels.
- Ex vivo infection inhibited tumor formation for over 100 days.
- Combination therapy with radiation led to complete tumor disappearance in xenograft models.
- Systemic delivery showed minimal, temporary liver function perturbation, indicating good safety.
Conclusions:
- A conditionally replicating adenovirus targeting EBV-positive NPC has been successfully developed.
- The adv.oriP.E1A therapy is effective in reducing tumor burden and shows a favorable safety profile.
- This EBV-dependent oncolytic virotherapy strategy holds significant therapeutic potential for NPC treatment.
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