Fraunhofer Institute for Interfacial Engineering and Biotechnology IGBIn order to optimize oncolytic viruses for therapeutic use, a consortium of the Fraunhofer Institutes ITEM, ISC, IZI, and ITWM, coordinated by Fraunhofer IGB, have developed a broadly applicable platform technology for combined oncolytic virus immunotherapy in the TheraVision project. An oncolytic virus for the treatment of non-small cell lung cancer has been developed as a proof of concept.
TheraVision – Platform technology for the development, production and testing of oncolytic viruses
Cell destruction (plaque formation) after infection of cells with green fluorescent HSV1 viruses.
Initial situation
Viruses are able to penetrate cells, produce both foreign and viral proteins, multiply, and ultimately kill infected cells, raising new hope in cancer therapy. Clinical trials involving first oncolytic (cancer-killing) viruses are very promising, although there is still a significant need for their optimization. This includes the development of viruses with increased specificity and efficacy, scalable and robust methods for their production, and models for their preclinical testing.
Objective
In the TheraVision project, the Fraunhofer Institutes ITEM, ISC, IZI, and ITWM, coordinated by Fraunhofer IGB, aim to establish a broadly applicable platform technology based on Herpes simplex virus type 1 (HSV1) for combinatorial oncolytic virus immunotherapy. As proof of concept, an oncolytic virus is being developed for the therapy of Non-Small Cell Lung Cancer (NSCLC).
Engineering of therapeutic virus vectors by modular functionalization of a platform vector
Genetic modification was used to establish an HSV1 platform vector that can be functionalized into an oncolytic drug transporter by insertion of transgenes. High specificity is achieved by targeting viruses to cancer cells, and efficacy is enhanced by expression of immunomodulators. Diverse foreign antigens that may contribute to tumor vaccination could finally be expressed in a virus-mediated manner.
Production of the viruses according to GMP guidelines
For the production of such a virus, a robust and scalable process has been developed simultaneously, which was optimized by bioinformatic modeling. This process addresses the regulatory stipulations of Good Manufacturing Practice (GMP) to allow for a seamless transfer to GMP production.
Testing with preclinical in-vitro and in-vivo models
For preclinical validation of therapeutic viruses, new models have been established that are suitable for investigating therapeutic effects on primary tumors as well as metastases in the presence of human immune cells. These range from human 3D in vitro tumor models to increasingly complex humanized in vivo mouse models.
Publications
[1] Bailer, S.M.; Funk, C.; Riedl, A.; Ruzsics, Z. (2017) Herpesviral vectors and their application in oncolytic therapy, vaccination, and gene transfer, Virus Genes 53(5): 741–748, DOI: 10.1007/s11262-017-1482-7
http://publica.fraunhofer.de/dokumente/N-455785.html
[2] Bailer, S.M. (2021) TheraVision – An oncolytic virus platform technology, European Biotechnology 20: 36
Project information
Project title
TheraVision – Platform technology for the development, production and testing of oncolytic viruses
Project duration
April 2017 – March 2020
Project partners
- Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart (Coordinator)
- Fraunhofer Institute for Toxicology and Experimental Medicine, Braunschweig and Regensburg
- Fraunhofer Institute for Silicate Research ISC, Würzburg
- Fraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig
- Fraunhofer Institute for Industrial Mathematics ITWM, Kaiserslautern
Funding
We would like to thank the Fraunhofer-Gesellschaft for funding the TheraVision project.