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Development of adenovirus-based oncolytic virus to induce EBV lytic reactivation

Sun Hee Lee1, Hyeji Byun1, Donghyun Seo1

  • 1Healthcare Convergence Educational Group for Infectious Disease Management, Vessel-Organ Interaction Research Center, Research Institute of Pharmaceutical Science, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu, 702-701, Republic of Korea.

Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
|September 30, 2025
PubMed
Abstract

Insights

A novel oncolytic adenovirus, Ad-TBZ, shows potent antitumor activity against Epstein-Barr virus-associated gastric cancer (EBVaGC). This engineered virus selectively targets and destroys EBVaGC cells, supporting its use as a monotherapy.

Area of Science:

  • Oncolytic virology
  • Cancer gene therapy
  • Gastroenterology

Background:

  • Epstein-Barr virus-associated gastric carcinoma (EBVaGC) accounts for ~10% of gastric cancers and presents therapeutic challenges.
  • Oncolytic viruses (OVs) are engineered to selectively replicate in and lyse tumor cells.

Purpose of the Study:

  • To develop and evaluate Ad-TBZ, a novel oncolytic adenovirus engineered for selective targeting of EBVaGC.
  • To investigate Ad-TBZ's ability to induce Epstein-Barr virus (EBV) lytic reactivation in tumor cells.

Main Methods:

  • Ad-TBZ was constructed with an hTERT promoter (hTERTp)-driven E1A/IRES-E1B cassette and a CMV promoter (CMVp)-driven BZLF1 gene.
  • Replication, cytotoxicity, and EBV lytic reactivation were assessed in EBVaGC cell lines, EBV-negative cells, and normal fibroblasts.
  • In vivo efficacy was evaluated in xenograft mouse models, with combination studies against platinum-based drugs and ganciclovir.

Main Results:

  • Ad-TBZ demonstrated selective replication and cytotoxicity in EBVaGC cells, sparing normal cells.
  • Significant upregulation of EBV lytic genes and increased viral genome copies were observed, leading to late apoptosis.
  • Ad-TBZ effectively suppressed tumor growth in vivo without systemic toxicity, indicating optimal performance as a monotherapy.

Conclusions:

  • Ad-TBZ exhibits potent and selective antitumor activity against EBVaGC via hTERTp-mediated replication and BZLF1-induced EBV lytic reactivation.
  • These findings support Ad-TBZ as a promising novel monotherapeutic strategy for EBVaGC.
Keywords:
AdenovirusBZLF1EBV-associated gastric cancerEpstein-Barr virusOncolytic virus

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