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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Latest insights into oncolytic viro-immunotherapy with vesicular stomatitis virus
Manuela Lizarralde-Guerrero1, David Olagnier2, Fernando Aranda3
1Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France; Université Paris-Saclay, Faculté de Médecine, Kremlin-Bicêtre, France.
Abstract:
Vesicular stomatitis virus (VSV), a rhabdovirus with intrinsic oncolytic properties, has emerged as a promising candidate for cancer therapy. Thanks to impaired antiviral responses affecting cancer cells, particularly downregulated type I interferon signaling, VSV selectively replicates in tumor cells while sparing normal cells. To mitigate neurotoxicity and improve therapeutic efficacy, genetically-engineered strains, such as VSV-∆M51, VSV-mIFNβ, and VSV-GP, have been developed. This review highlights the latest advances in VSV-based oncolytic virotherapy, focusing on novel modifications of the viral genome, as well as on combination strategies designed to enhance tumor selectivity, stimulate antitumor responses, and overcome resistance mechanisms. Recent studies have introduced modifications that bolster immunogenicity, and improve viral replication within tumors. Additionally, approaches combining VSV with small molecules, immune checkpoint inhibitors and other immunomodulatory agents, promise to augment antitumor activity. Emerging evidence suggests that VSV can reshape the tumor microenvironment, thus promoting robust adaptive antitumor immune responses. Ongoing research continues to explore strategies for improving systemic delivery, minimizing off-target effects, and enhancing viral persistence within the tumor bed. Further investigation and clinical translation will determine the full potential of VSV-based viroimmunotherapy in cancer treatment.
Insights
Vesicular stomatitis virus (VSV) shows promise for cancer therapy due to its ability to selectively target tumor cells. Genetically engineered VSV strains and combination therapies are being developed to enhance efficacy and overcome resistance.
Area of Science:
- Oncolytic virotherapy
- Cancer immunotherapy
- Virology
Background:
- Vesicular stomatitis virus (VSV), a rhabdovirus, possesses inherent oncolytic capabilities.
- Cancer cells often exhibit impaired antiviral responses, such as downregulated type I interferon signaling, enabling selective VSV replication.
- Genetically modified VSV strains (e.g., VSV-∆M51, VSV-mIFNβ, VSV-GP) are engineered to improve safety and efficacy.
Purpose of the Study:
- To review recent advancements in VSV-based oncolytic virotherapy.
- To explore novel viral genome modifications and combination strategies.
- To highlight VSV's potential in enhancing antitumor responses and overcoming resistance.
Main Methods:
- Review of recent scientific literature on VSV-based cancer therapy.
- Analysis of modifications to VSV genome to enhance immunogenicity and tumor replication.
- Examination of combination strategies involving VSV with other therapeutic agents.
Main Results:
- Modified VSV strains demonstrate enhanced immunogenicity and tumor replication.
- Combination therapies (VSV with small molecules, checkpoint inhibitors) show augmented antitumor activity.
- VSV can modulate the tumor microenvironment to promote adaptive immune responses.
Conclusions:
- VSV-based virotherapy is a promising approach for cancer treatment.
- Ongoing research focuses on improving delivery, reducing off-target effects, and enhancing viral persistence.
- Further clinical translation is needed to realize the full potential of VSV-based cancer therapies.
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