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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo

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Delivery Strategies for Oncolytic Viruses in Gastrointestinal Cancers: Progress, Mechanisms and Clinical Translations

Chi Xue1, Yanchen Liu2, Changxin Yin3

  • 1Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Hospital of China Medical University, Shenyang, China.

Reviews in Medical Virology
|July 31, 2026
PubMed

Insights

Strategies to enhance oncolytic virus (OV) delivery in gastrointestinal cancers involve genetic engineering, combination therapies, and carrier-mediated delivery. These approaches improve viral targeting, efficacy, and immune response against tumors.

Area of Science:

  • Oncology
  • Virology
  • Immunology

Background:

  • Gastrointestinal cancers present significant challenges for oncolytic virus (OV) therapy due to complex anatomy, tumor heterogeneity, and immunosuppressive microenvironments.
  • Effective delivery and function of OVs are severely restricted in these tumors, limiting therapeutic potential.

Purpose of the Study:

  • To review and summarize multidimensional strategies aimed at improving the efficiency of oncolytic virus delivery in gastrointestinal cancers.
  • To highlight advances in overcoming barriers to OV therapy in this challenging cancer type.

Main Methods:

  • Genetic engineering of OVs through gene deletion and therapeutic gene insertion to enhance targeting, safety, and capacity.
  • Combination therapies including radiotherapy, chemotherapy, and immunotherapy for microenvironmental preconditioning and improved viral distribution.
  • Modulation of the tumor immune microenvironment to promote viral replication and spread, especially in 'cold' tumors.
  • Carrier-mediated delivery systems such as stem cells, extracellular vesicles, and viral envelope reconstitution to overcome systemic delivery barriers.

Main Results:

  • Genetic engineering significantly enhances OV targeting, safety, and therapeutic capacity.
  • Combination therapies improve viral distribution, local accumulation, and immune activation within tumors.
  • Immune microenvironment modulation boosts viral replication and spread, inducing systemic anti-tumor responses.
  • Carrier-mediated delivery offers innovative solutions for systemic OV delivery challenges.

Conclusions:

  • Despite challenges like rapid clearance and viral inactivation, reviewed strategies show significant progress in OV delivery mechanisms, immune synergy, and targeted accumulation.
  • These advances provide a strong foundation and new directions for the clinical translation of oncolytic viruses in gastrointestinal tumors.
Keywords:
antitumour immunitycombination regimendelivery strategiesimmuno‐oncologyoncolytic virus

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