Anatomical and physical barriers to tumor targeting with oncolytic adenoviruses in vivo
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Updated: Jun 19, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
1University of Washington, Division of Medical Genetics, Seattle, WA 98195, USA.
Abstract:
Despite promising results in preclinical studies, the therapeutic efficacy of oncolytic adenoviruses (Ads) has not been reproduced in clinical trials in patients with cancer. Recent studies have identified several obstacles that limit the therapeutic efficacy of oncolytic Ads. These obstacles include the lack of a primary Ad attachment receptor on tumor cells in situ, as well as innate host defense mechanisms that recognize Ads as pathogens and act to facilitate their elimination. This review focuses on anatomical barriers inside solid tumors that limit Ad transduction, and specifically barriers associated with several factors: (i) the mechanisms of tumor vascularization and the metabolic microenvironment; (ii) the tumor stroma, which tightly surrounds nests of malignant cells; and (iii) the epithelial phenotype of cancer cells, particularly the trapping of viral receptors in tight and adherens junctions. Potential strategies to overcome these obstacles are also presented. Because published data on the physical barriers to Ad transduction of tumors in situ are limited, studies with other macromolecules used in tumor therapy are also discussed.
Insights
Oncolytic adenoviruses (Ads) show promise but face clinical challenges due to tumor barriers. Overcoming these physical and immune obstacles is key to improving Ad cancer therapy efficacy.
Area of Science:
- Oncolytic virotherapy
- Cancer biology
- Viral immunology
Background:
- Preclinical studies show promise for oncolytic adenoviruses (Ads) in cancer therapy.
- Clinical efficacy of Ads has been limited by several obstacles.
- These include lack of primary Ad attachment receptors and host immune responses.
Purpose of the Study:
- To review anatomical barriers limiting oncolytic Ad transduction in solid tumors.
- To discuss factors contributing to these barriers, including tumor vascularization, microenvironment, stroma, and cancer cell phenotype.
- To present potential strategies for overcoming these obstacles.
Main Methods:
- Review of existing literature on oncolytic Ad therapy.
- Analysis of anatomical and biological barriers within solid tumors.
- Discussion of strategies to enhance Ad tumor cell transduction.
- Inclusion of studies on other macromolecules in tumor therapy due to limited Ad-specific data.
Main Results:
- Solid tumors present significant physical barriers to Ad transduction.
- Key barriers include tumor vascularization, metabolic microenvironment, dense stroma, and epithelial cell junctions.
- Host immune responses also contribute to Ad elimination.
- Strategies to overcome these barriers are being explored.
Conclusions:
- Anatomical and biological barriers significantly impede oncolytic Ad efficacy in solid tumors.
- Understanding these limitations is crucial for developing improved Ad-based cancer therapies.
- Further research into overcoming these barriers may enhance oncolytic virotherapy outcomes.
