TheraVision: Engineering platform technology for the development of oncolytic viruses based on herpes simplex virus...

Area of Science:

• Oncolytic virotherapy
• Cancer immunotherapy
• Genetic engineering

Background:

• Oncolytic viruses (OVs) show promise in cancer therapy by selectively killing tumor cells and stimulating anti-tumor immunity.
• Current OVs require optimization for improved safety and efficacy.
• Combinatorial approaches integrating OVs with immunotherapies are needed.

Purpose of the Study:

• To develop a versatile engineering platform for creating combinatorial oncolytic virus and immunotherapy agents.
• To generate an attenuated herpes simplex virus type 1 (HSV1)-based OV with enhanced safety and modularity.
• To demonstrate the platform's capability in generating armed OVs with dual therapeutic functions.

Main Methods:

• Genetic engineering of an attenuated herpes simplex virus type 1 (HSV1) strain.
• Integration of transgenes encoding single-chain variable fragments (scFvs) for EGFR targeting and PD-1 blockade.
• Preclinical evaluation in patient-derived organoids, 3D tumor models, and humanized mouse models.

Main Results:

• An engineered HSV1-based OV selectively targeted EGFR-expressing tumor cells.
• The OV produced a functional PD-1 immune checkpoint inhibitor, combining oncolysis and immunotherapy.
• Demonstrated safety and efficacy in diverse preclinical cancer models.

Conclusions:

• A novel, proprietary engineering platform based on HSV1 has been established for oncolytic virotherapy.
• The platform facilitates the generation of armed OVs with combined oncolytic and immunotherapeutic properties.
• This technology enables streamlined preclinical development of advanced oncolytic virus-based cancer treatments.