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Updated: Aug 6, 2025

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
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Targeting carcinoembryonic antigen-expressing tumors using a novel transcriptional and translational dual-regulated

Dmitry V Chouljenko1, Yanal M Murad1, I-Fang Lee1

  • 1Virogin Biotech Canada Ltd., 150-13511 Commerce Parkway, Richmond, BC V6V 2J8, Canada.

Molecular Therapy Oncolytics
|March 20, 2023
PubMed

Insights

VG2025, a novel oncolytic herpes simplex virus type 1 (HSV-1), demonstrates enhanced tumor-specific replication and potent antitumor effects. This engineered virus shows excellent safety and potential for biomarker-guided precision medicine in cancer therapy.

Area of Science:

  • Oncolytic virotherapy
  • Gene therapy
  • Immunotherapy

Background:

  • Recombinant oncolytic herpes simplex virus type 1 (HSV-1) engineered for enhanced safety and tumor-specific replication.
  • Transcriptional and translational dual regulation (TTDR) platform for precise control of viral gene expression.
  • Incorporation of immune-stimulating cytokines (IL-12, IL-15/IL-15Rα) to augment anti-tumor immune responses.

Purpose of the Study:

  • To evaluate the safety and efficacy of VG2025, a novel TTDR-engineered oncolytic HSV-1.
  • To assess the tumor-specific replication and anti-tumor immune response induced by VG2025.
  • To investigate the potential of VG2025 in biomarker-based precision medicine.

Main Methods:

  • Development of VG2025 utilizing TTDR, including a CEA promoter for ICP27 and miR-binding sites for ICP34.5.
  • In vitro validation of TTDR selectivity and in vivo efficacy studies via intratumoral and intravenous administration.
  • Analysis of tumor gene expression, immune cell infiltration, and assessment of neurotoxicity in preclinical models.

Main Results:

  • VG2025 demonstrated high selectivity and potent in vivo antitumor efficacy with both administration routes.
  • Significant abscopal effects and immune memory responses were observed, indicating a robust anti-tumor immune activation.
  • Tumor treatment led to increased immune cell infiltration and activation of immune-signaling pathways, with no observed neurotoxicity in mice or non-human primates.

Conclusions:

  • VG2025 exhibits enhanced tumor clearance and an excellent safety profile, supporting its potential as an oncolytic virotherapy agent.
  • The correlation between CEA levels and viral replication efficiency suggests VG2025's suitability for biomarker-based precision medicine.
  • VG2025 represents a promising advancement in oncolytic virotherapy, offering targeted tumor destruction and immune stimulation with improved safety.
Keywords:
HSV-1VG2025cancer vaccineimmunotherapyinterleukin-12interleukin-15intravenous deliverymicroRNAoncolytic virusvirotherapy

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