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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Strategies to enhance viral penetration of solid tumors
Elspeth Smith1, Jessica Breznik, Brian D Lichty
1Centre for Gene Therapeutics, McMaster University, Hamilton, ON, Canada L8N 3Z5.
Abstract:
The efficient delivery of viral vectors to tumors is an active area of investigation. A number of barriers exist that must be overcome to achieve good penetration of vectors into tumors and distribution of their effects throughout the tumor mass. Replicating oncolytic viruses have the advantage of being able to amplify the initial dose, but progeny virus are prevented from spreading because of a dense mass of tightly packed cells with a dense extracellular matrix, admixed normal stromal cells, and high interstitial pressure. Although intratumoral injection may ensure initial delivery the distribution achieved by intravenous administration may be superior and come with beneficial bystander damage to the tumor vasculature. Strategies to enhance intravenous delivery and subsequent spread of these vectors within tumors are being developed by a number of groups. Achieving the goal of efficient penetration and spread of viruses within solid tumors is a necessary prerequisite to significant improvements in virus-vectored therapy of solid tumors.
Insights
Efficient delivery of viral vectors to solid tumors remains a challenge. Strategies are being developed to overcome barriers and improve the spread of oncolytic viruses for better cancer therapy.
Area of Science:
- Oncology
- Virology
- Biomedical Engineering
Background:
- Efficient delivery of viral vectors to tumors is crucial for effective cancer therapy.
- Solid tumors present significant barriers to vector penetration and distribution.
- Replicating oncolytic viruses offer potential for in-situ dose amplification.
Purpose of the Study:
- To review the challenges in achieving efficient viral vector delivery and spread within solid tumors.
- To discuss strategies aimed at enhancing the penetration and distribution of oncolytic viruses.
- To highlight the importance of overcoming tumor microenvironment barriers for improved virus-vectored therapies.
Main Methods:
- Review of current research on viral vector delivery to tumors.
- Analysis of barriers to viral vector penetration and spread in solid tumors.
- Discussion of strategies for enhancing intravenous and intratumoral delivery of oncolytic viruses.
Main Results:
- Tumor microenvironment factors like dense extracellular matrix and high interstitial pressure impede viral spread.
- Intratumoral injection ensures initial delivery but may limit distribution.
- Intravenous administration offers potential for superior distribution and tumor vasculature damage.
Conclusions:
- Overcoming barriers to viral vector penetration and spread is essential for advancing virus-vectored cancer therapy.
- Developing strategies to enhance viral vector delivery is a key area of ongoing research.
- Improved delivery and distribution are prerequisites for significant therapeutic improvements in solid tumors.
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