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TheraVision: Engineering platform technology for the development of oncolytic viruses based on herpes simplex virus
Christina Funk1, Nadja Uhlig2, Zsolt Ruzsics3
1Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany.
Abstract:
Viruses are able to efficiently penetrate cells, multiply, and eventually kill infected cells, release tumor antigens, and activate the immune system. Therefore, viruses are highly attractive novel agents for cancer therapy. Clinical trials with first generations of oncolytic viruses (OVs) are very promising but show significant need for optimization. The aim of TheraVision was to establish a broadly applicable engineering platform technology for combinatorial oncolytic virus and immunotherapy. Through genetic engineering, an attenuated herpes simplex virus type 1 (HSV1) was generated that showed increased safety compared to the wild-type strain. To demonstrate the modularity and the facilitated generation of new OVs, two transgenes encoding retargeting as well as immunomodulating single-chain variable fragments (scFvs) were integrated into the platform vector. The resulting virus selectively infected epidermal growth factor receptor (EGFR)-expressing cells and produced a functional immune checkpoint inhibitor against programmed cell death protein 1 (PD-1). Thus, both viral-mediated oncolysis and immune-cell-mediated therapy were combined into a single viral vector. Safety and functionality of the armed OVs have been shown in novel preclinical models ranging from patient-derived organoids and tissue-engineered human in vitro 3D tumor models to complex humanized mouse models. Consequently, a novel and proprietary engineering platform vector based on HSV1 is available for the facilitated preclinical development of oncolytic virotherapy.
Insights
Researchers engineered a novel oncolytic virus (OV) platform using herpes simplex virus type 1 (HSV1) for enhanced cancer therapy. This platform combines viral oncolysis with immunotherapy, showing promise in preclinical models.
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.
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