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Updated: Aug 14, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Oncolytic virotherapy: approaches to tumor targeting and enhancing antitumor effects
Stephen H Thorne1, Terry Hermiston, David Kirn
1Department of Pediatrics and Bio-X Program, Stanford University School of Medicine, Stanford, CA 94305-5427, USA. sthorne@stanford.edu
Abstract:
The application of replicating viruses for the treatment of cancers represents a novel therapy that is distinct from traditional treatment modalities. It is apparent that the genetic changes that a virus produces within an infected cell in order to create an environment conducive to viral replication are often similar to the processes involved in cellular transformation. These include uncontrolled cellular proliferation, prevention of apoptosis, and resistance to host organism immune effector mechanisms. Deletions of viral genes involved in these processes have been exploited to produce viral mutants whose replication is selective for transformed cells. The use of tissue-specific transcriptional response or RNA stability elements to control the expression of critical viral genes has also resulted in targeted viruses. Work also is being undertaken to restrict or alter the tropism of viruses by altering their ability to infect certain cell types. Finally, the addition of exogenous genes can be used to increase the virus's lytic potential and/or bystander killing; to further induce the host's immune response against cancer cells; and/or to permit the controlled downregulation of viral replication if necessary. The combination of different tumor-targeting mutations in parallel with the expression of foreign genes has resulted in the evolution of second- and third-generation viruses that continue to become further distinct from their native parental strains. The movement of these viruses into the clinic has begun to demonstrate the potential of this approach in the treatment of cancers.
Insights
Oncolytic viruses, engineered to selectively replicate in cancer cells, offer a novel therapeutic approach. These modified viruses exploit cancer
Area of Science:
- Oncology
- Virology
- Biotechnology
Background:
- Cancer development involves genetic changes that share similarities with viral replication processes.
- Traditional cancer therapies have limitations, necessitating novel treatment strategies.
- Viruses possess inherent mechanisms that can be harnessed for anti-cancer applications.
Purpose of the Study:
- To explore the potential of replicating viruses as a novel cancer therapy.
- To discuss the genetic modifications employed to create tumor-selective viruses.
- To highlight the advancements in oncolytic virus development and clinical translation.
Main Methods:
- Engineering viral mutants with deletions in genes promoting viral replication and cellular transformation.
- Utilizing tissue-specific elements to control viral gene expression and target cancer cells.
- Modifying viral tropism to restrict infection to specific cell types.
- Introducing exogenous genes to enhance viral lytic activity, immune response, and replication control.
Main Results:
- Development of tumor-selective viral mutants through gene deletions.
- Creation of targeted viruses using transcriptional or RNA stability elements.
- Advancements in altering viral tropism for enhanced cancer cell targeting.
- Evolution of second- and third-generation oncolytic viruses with combined tumor-targeting mutations and foreign gene expression.
Conclusions:
- Oncolytic virus therapy represents a promising new modality distinct from conventional treatments.
- Genetic engineering of viruses allows for selective replication in cancer cells, minimizing harm to healthy tissues.
- Clinical trials are beginning to demonstrate the therapeutic potential of oncolytic viruses in cancer treatment.
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