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Oncolytic Virotherapy: A Contest between Apples and Oranges
Stephen J Russell1, Kah-Whye Peng1
1Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Abstract:
Viruses can be engineered or adapted for selective propagation in neoplastic tissues and further modified for therapeutic transgene expression to enhance their antitumor potency and druggability. Oncolytic viruses (OVs) can be administered locally or intravenously and spread to a variable degree at sites of tumor growth. OV-infected tumor cells die in situ, releasing viral and tumor antigens that are phagocytosed by macrophages, transported to regional lymph nodes, and presented to antigen-reactive T cells, which proliferate before dispersing to kill uninfected tumor cells at distant sites. Several OVs are showing clinical promise, and one of them, talimogene laherparepvec (T-VEC), was recently granted marketing approval for intratumoral therapy of nonresectable metastatic melanoma. T-VEC also appears to substantially enhance clinical responsiveness to checkpoint inhibitor antibody therapy. Here, we examine the T-VEC paradigm and review some of the approaches currently being pursued to develop the next generation of OVs for both local and systemic administration, as well as for use in combination with other immunomodulatory agents.
Insights
Oncolytic viruses (OVs) are engineered to target and destroy cancer cells, stimulating an immune response against tumors. The study reviews the progress and future directions of OV therapies, including talimogene laherparepvec (T-VEC).
Area of Science:
- Oncolytic virotherapy
- Cancer immunotherapy
- Viral oncology
Background:
- Viruses can be engineered for selective replication in tumors and modified for therapeutic transgene expression.
- Oncolytic viruses (OVs) are administered locally or intravenously, spreading within tumor sites.
- OV-infected tumor cells release antigens, initiating an immune response against cancer cells.
Purpose of the Study:
- To examine the talimogene laherparepvec (T-VEC) paradigm in oncolytic virotherapy.
- To review the development of next-generation OVs for cancer treatment.
- To explore the combination of OVs with immunomodulatory agents.
Main Methods:
- Review of clinical data and research on oncolytic viruses.
- Analysis of talimogene laherparepvec (T-VEC) as a therapeutic model.
- Examination of strategies for developing novel OVs for local and systemic administration.
Main Results:
- Oncolytic viruses demonstrate potential in cancer treatment, with T-VEC approved for melanoma.
- T-VEC enhances responsiveness to checkpoint inhibitor therapy.
- Ongoing research focuses on next-generation OVs and combination therapies.
Conclusions:
- Oncolytic viruses represent a promising therapeutic strategy for cancer.
- Talimogene laherparepvec (T-VEC) highlights the clinical success of OV therapy.
- Future directions include developing advanced OVs and combining them with other immunotherapies for improved antitumor efficacy.