Employing the Oncolytic Vesicular Stomatitis Virus in Cancer Virotherapy: Resistance and Clinical Considerations

Area of Science:

• Virology
• Oncology
• Immunology

Background:

• Vesicular Stomatitis Virus (VSV) is a versatile viral vector with applications in vaccines, gene delivery, and oncolytic virotherapy.
• Despite its potential, resistance to VSV-mediated oncolysis in certain cancers hinders its clinical effectiveness.
• Understanding resistance mechanisms is crucial for optimizing VSV-based cancer treatments.

Purpose of the Study:

• To review recent advancements in VSV-based oncolysis.
• To analyze mechanisms of resistance to VSV oncolysis.
• To discuss strategies for overcoming resistance and enhancing therapeutic efficacy.

Main Methods:

• Literature review of recent studies on VSV oncolysis.
• Analysis of resistance mechanisms including IFN signaling, ISGs, TME, and tumor-intrinsic factors.
• Evaluation of strategies to overcome resistance, such as enhancing viral selectivity and combination therapies.

Main Results:

• Key resistance mechanisms identified: sustained type-I IFN signaling, ISG upregulation, immune cell activation, tumor microenvironment (TME) factors, and tumor-intrinsic properties.
• Strategies to overcome resistance include improving viral oncoselectivity, inhibiting IFN responses, TME modulation, and combining VSV with chemotherapy, radiation, or immune checkpoint inhibitors.
• Promising results from VSV-based Phase I/II clinical trials, underscoring the need to address resistance.

Conclusions:

• Addressing resistance mechanisms is essential for realizing the full therapeutic potential of VSV oncolytic virotherapy.
• Future research should prioritize patient-specific approaches and personalized treatments based on tumor molecular profiles.
• Identifying predictive biomarkers for VSV oncolysis resistance will improve patient selection and treatment efficacy.