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Strategies for enhancing intratumoral spread of oncolytic adenoviruses
Nasser Hashemi Goradel1, Babak Negahdari1, Sajjad Ghorghanlu1
1Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:
Oncolytic viruses, effectively replicate viruses within malignant cells to lyse them without affecting normal ones, have recently shown great promise in developing therapeutic options for cancer. Adenoviruses (Ads) are one of the candidates in oncolytic virotheraoy due to its easily manipulated genomic DNA and expression of wide rane of its receptors on the various cancers. Although systematic delivery of oncolytic adenoviruses can target both primary and metastatic tumors, there are some drawbacks in the effective systematic delivery of oncolytic adenoviruses, including pre-existing antibodies and liver tropism. To overcome these limitations, intratumural (IT) administration of oncolytic viruses have been proposed. However, IT injection of Ads leaves much of the tumor mass unaffected and Ads are not able to disperse more in the tumor microenvironment (TME). To this end, various strategies have been developed to enhance the IT spread of oncolytic adenoviruses, such as using extracellular matrix degradation enzymes, junction opening peptides, and fusogenic proteins. In the present paper, we reviewed different oncolytic adenoviruses, their application in the clinical trials, and strategies for enhancing their IT spread.
Insights
Oncolytic adenoviruses show promise for cancer therapy. Strategies are reviewed to improve their spread within tumors after intratumoral injection, enhancing treatment effectiveness.
Area of Science:
- Oncolytic virotherapy
- Cancer therapeutics
- Viral oncology
Background:
- Oncolytic viruses replicate in cancer cells, selectively destroying them.
- Adenoviruses are promising oncolytic agents due to genetic manipulability and receptor expression on tumors.
- Systemic delivery faces challenges like pre-existing antibodies and liver tropism, leading to interest in intratumoral (IT) administration.
Purpose of the Study:
- To review oncolytic adenoviruses and their clinical applications.
- To explore strategies for enhancing IT delivery and tumor penetration of adenoviruses.
- To address limitations of current oncolytic adenovirus therapies.
Main Methods:
- Review of existing literature on oncolytic adenoviruses.
- Analysis of clinical trial data for oncolytic adenovirus therapies.
- Examination of methods to improve intratumoral spread, including extracellular matrix degradation, junction opening peptides, and fusogenic proteins.
Main Results:
- Adenoviruses are viable candidates for oncolytic virotherapy.
- Intratumoral administration is an alternative to systemic delivery but faces challenges in tumor penetration.
- Various strategies show potential to enhance adenovirus spread within the tumor microenvironment.
Conclusions:
- Oncolytic adenoviruses offer a promising approach to cancer treatment.
- Enhancing intratumoral spread is crucial for maximizing the efficacy of oncolytic adenoviruses.
- Further research into novel delivery strategies is essential for advancing oncolytic virotherapy.
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