TheraVision: Engineering platform technology for the development of oncolytic viruses based on herpes simplex virus type 1
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...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-03-01
|
| Series: | Molecular Therapy: Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329924000262 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850162616156028928 |
|---|---|
| author | Christina Funk Nadja Uhlig Zsolt Ruzsics Florentin Baur Matthias Peindl Sarah Nietzer Karina Epting Gabriele Vacun Gudrun Dandekar Catherine Botteron Christian Werno Thomas Grunwald Susanne M. Bailer |
| author_facet | Christina Funk Nadja Uhlig Zsolt Ruzsics Florentin Baur Matthias Peindl Sarah Nietzer Karina Epting Gabriele Vacun Gudrun Dandekar Catherine Botteron Christian Werno Thomas Grunwald Susanne M. Bailer |
| author_sort | Christina Funk |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c026db125d4b4ec9b073d1f2aad9f3c3 |
| institution | OA Journals |
| issn | 2950-3299 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-c026db125d4b4ec9b073d1f2aad9f3c32025-08-20T02:22:32ZengElsevierMolecular Therapy: Oncology2950-32992024-03-0132120078410.1016/j.omton.2024.200784TheraVision: Engineering platform technology for the development of oncolytic viruses based on herpes simplex virus type 1Christina Funk0Nadja Uhlig1Zsolt Ruzsics2Florentin Baur3Matthias Peindl4Sarah Nietzer5Karina Epting6Gabriele Vacun7Gudrun Dandekar8Catherine Botteron9Christian Werno10Thomas Grunwald11Susanne M. Bailer12Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, GermanyFraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, GermanyDepartment for Medical Microbiology and Hygiene, Institute of Virology, University Medical Center Freiburg, Freiburg, GermanyChair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Röntgenring, Würzburg, GermanyChair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Röntgenring, Würzburg, GermanyChair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Röntgenring, Würzburg, Germany; Fraunhofer Institute for Silicate Research ISC, Translational Center Regenerative Therapies, Würzburg, GermanyFraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, GermanyFraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, GermanyChair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Röntgenring, Würzburg, Germany; Fraunhofer Institute for Silicate Research ISC, Translational Center Regenerative Therapies, Würzburg, GermanyFraunhofer Institute for Toxicology and Experimental Medicine, Regensburg, GermanyFraunhofer Institute for Toxicology and Experimental Medicine, Regensburg, GermanyFraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, GermanyFraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany; Corresponding author: Susanne M. Bailer, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Nobelstraße 12, 70569 Stuttgart, Germany.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.http://www.sciencedirect.com/science/article/pii/S2950329924000262MT: Regular Issueoncolytic virotherapycombined virus immunotherapytumor therapyNSCLCvirus engineering |
| spellingShingle | Christina Funk Nadja Uhlig Zsolt Ruzsics Florentin Baur Matthias Peindl Sarah Nietzer Karina Epting Gabriele Vacun Gudrun Dandekar Catherine Botteron Christian Werno Thomas Grunwald Susanne M. Bailer TheraVision: Engineering platform technology for the development of oncolytic viruses based on herpes simplex virus type 1 Molecular Therapy: Oncology MT: Regular Issue oncolytic virotherapy combined virus immunotherapy tumor therapy NSCLC virus engineering |
| title | TheraVision: Engineering platform technology for the development of oncolytic viruses based on herpes simplex virus type 1 |
| title_full | TheraVision: Engineering platform technology for the development of oncolytic viruses based on herpes simplex virus type 1 |
| title_fullStr | TheraVision: Engineering platform technology for the development of oncolytic viruses based on herpes simplex virus type 1 |
| title_full_unstemmed | TheraVision: Engineering platform technology for the development of oncolytic viruses based on herpes simplex virus type 1 |
| title_short | TheraVision: Engineering platform technology for the development of oncolytic viruses based on herpes simplex virus type 1 |
| title_sort | theravision engineering platform technology for the development of oncolytic viruses based on herpes simplex virus type 1 |
| topic | MT: Regular Issue oncolytic virotherapy combined virus immunotherapy tumor therapy NSCLC virus engineering |
| url | http://www.sciencedirect.com/science/article/pii/S2950329924000262 |
| work_keys_str_mv | AT christinafunk theravisionengineeringplatformtechnologyforthedevelopmentofoncolyticvirusesbasedonherpessimplexvirustype1 AT nadjauhlig theravisionengineeringplatformtechnologyforthedevelopmentofoncolyticvirusesbasedonherpessimplexvirustype1 AT zsoltruzsics theravisionengineeringplatformtechnologyforthedevelopmentofoncolyticvirusesbasedonherpessimplexvirustype1 AT florentinbaur theravisionengineeringplatformtechnologyforthedevelopmentofoncolyticvirusesbasedonherpessimplexvirustype1 AT matthiaspeindl theravisionengineeringplatformtechnologyforthedevelopmentofoncolyticvirusesbasedonherpessimplexvirustype1 AT sarahnietzer theravisionengineeringplatformtechnologyforthedevelopmentofoncolyticvirusesbasedonherpessimplexvirustype1 AT karinaepting theravisionengineeringplatformtechnologyforthedevelopmentofoncolyticvirusesbasedonherpessimplexvirustype1 AT gabrielevacun theravisionengineeringplatformtechnologyforthedevelopmentofoncolyticvirusesbasedonherpessimplexvirustype1 AT gudrundandekar theravisionengineeringplatformtechnologyforthedevelopmentofoncolyticvirusesbasedonherpessimplexvirustype1 AT catherinebotteron theravisionengineeringplatformtechnologyforthedevelopmentofoncolyticvirusesbasedonherpessimplexvirustype1 AT christianwerno theravisionengineeringplatformtechnologyforthedevelopmentofoncolyticvirusesbasedonherpessimplexvirustype1 AT thomasgrunwald theravisionengineeringplatformtechnologyforthedevelopmentofoncolyticvirusesbasedonherpessimplexvirustype1 AT susannembailer theravisionengineeringplatformtechnologyforthedevelopmentofoncolyticvirusesbasedonherpessimplexvirustype1 |