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Published on: January 7, 2019
Oncolytic virotherapy
Stephen J Russell1, Kah-Whye Peng, John C Bell
1Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA. sjr@mayo.edu
Abstract:
Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancers. Recent advances include preclinical proof of feasibility for a single-shot virotherapy cure, identification of drugs that accelerate intratumoral virus propagation, strategies to maximize the immunotherapeutic action of oncolytic viruses and clinical confirmation of a critical viremic threshold for vascular delivery and intratumoral virus replication. The primary clinical milestone has been completion of accrual in a phase 3 trial of intratumoral herpes simplex virus therapy using talimogene laherparepvec for metastatic melanoma. Key challenges for the field are to select 'winners' from a burgeoning number of oncolytic platforms and engineered derivatives, to transiently suppress but then unleash the power of the immune system to maximize both virus spread and anticancer immunity, to develop more meaningful preclinical virotherapy models and to manufacture viruses with orders-of-magnitude higher yields than is currently possible.
Insights
Oncolytic virotherapy uses cancer-killing viruses. Advances show promise for cures, improved virus spread, and enhanced immune response, with a key trial in melanoma nearing completion.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Oncolytic virotherapy utilizes replication-competent viruses as a novel cancer treatment.
- Recent progress includes preclinical validation of single-administration cures and enhanced intratumoral virus propagation.
Purpose of the Study:
- To summarize recent advances in oncolytic virotherapy.
- To highlight key milestones and challenges in the field.
Main Methods:
- Review of preclinical studies demonstrating feasibility and drug potentiation.
- Analysis of strategies for optimizing immunotherapeutic effects.
- Examination of clinical trial data, including a Phase 3 trial for metastatic melanoma.
Main Results:
- Preclinical proof-of-concept for single-shot virotherapy cures.
- Identification of drugs accelerating virus spread within tumors.
- Clinical confirmation of a viremic threshold for effective viral delivery and replication.
- Completion of accrual for a Phase 3 trial of talimogene laherparepvec for melanoma.
Conclusions:
- Oncolytic virotherapy is a rapidly advancing field with significant clinical progress.
- Key challenges include platform selection, immune system modulation, improved preclinical models, and scalable manufacturing.
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