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Oncolytic virus immunotherapies in ovarian cancer: moving beyond adenoviruses
Joseph Hoare1, Nicola Campbell1, Elisabete Carapuça1
1Centre for Molecular Oncology, Barts Cancer Institute - a CRUK Centre of Excellence, Queen Mary University of London, London, United Kingdom.
Abstract:
Ovarian cancer is the 5th most common cancer in UK women with a high relapse rate. The overall survival for ovarian cancer has remained low for decades prompting a real need for new therapies. Recurrent ovarian cancer remains confined in the peritoneal cavity in >80% of the patients, providing an opportunity for locoregional administration of novel therapeutics, including gene and viral therapy approaches. Immunotherapy is an expanding field, and includes oncolytic viruses as well as monoclonal antibodies, immune checkpoint inhibitors, and therapeutic vaccines. Oncolytic viruses cause direct cancer cell cytolysis and immunogenic cell death and subsequent release of tumor antigens that will prime for a potent tumor-specific immunity. This effect may be further enhanced when the viruses are engineered to express, or coadministered with, immunostimulatory molecules. Currently, the most commonly used and well-characterized vectors utilized for virotherapy purposes are adenoviruses. They have been shown to work synergistically with traditional chemotherapy and radiotherapy and have met with success in clinical trials. However, pre-existing immunity and poor in vivo models limit our ability to fully investigate the potential of oncolytic adenovirus as effective immunotherapies which in turn fosters the need to develop alternative viral vectors. In this review we cover recent advances in adenovirus-based oncolytic therapies targeting ovarian cancer and recent advances in mapping immune responses to oncolytic virus therapies in ovarian cancer.
Insights
New ovarian cancer therapies are needed due to high relapse rates. Oncolytic viruses, particularly adenoviruses, show promise for locoregional treatment, enhancing anti-tumor immunity.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Ovarian cancer is a leading cause of cancer death in UK women, characterized by high recurrence rates and limited treatment options.
- Locoregional therapies are promising for recurrent ovarian cancer, which often remains confined to the peritoneal cavity.
- Immunotherapy, including oncolytic viruses, offers a novel approach to combat ovarian cancer by stimulating anti-tumor immune responses.
Purpose of the Study:
- To review recent advances in adenovirus-based oncolytic therapies for ovarian cancer.
- To discuss the mapping of immune responses to oncolytic virus therapies in ovarian cancer.
- To highlight the potential of oncolytic viruses as a therapeutic strategy for ovarian cancer.
Main Methods:
- Review of current literature on adenovirus-based oncolytic virotherapy for ovarian cancer.
- Analysis of studies investigating immune responses to oncolytic virus treatments.
- Exploration of synergistic effects with chemotherapy and radiotherapy.
Main Results:
- Adenoviruses are well-characterized vectors for virotherapy, demonstrating synergy with conventional treatments.
- Oncolytic viruses induce direct cancer cell death and immunogenic cell death, releasing tumor antigens to prime immunity.
- Engineered viruses or co-administration with immunostimulatory molecules can enhance therapeutic effects.
Conclusions:
- Adenovirus-based oncolytic therapies represent a promising avenue for ovarian cancer treatment.
- Understanding and mapping immune responses are crucial for optimizing oncolytic virus efficacy.
- Further research into alternative viral vectors is warranted due to limitations of adenoviruses, such as pre-existing immunity.
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