TheraVision – viruses against cancer

Viruses have great potential in cancer therapy: they are capable of efficiently penetrating cells, produce their own proteins, multiply, and ultimately kill the infected cells. Clinical studies on oncolytic (cancer-killing) viruses are very promising. However, there is a significant need for optimization with regard to virus specificity and efficacy, production methods, and models for preclinical testing.

Structured in three pillars

The TheraVision project is establishing a broadly applicable platform technology for combinatorial oncolytic virus-immunotherapy based on three pillars.

1  Engineering of therapeutic virus vectors

An HSV1 platform vector was established by genetic engineering and in the next step will be functionalized as an oncolytic virus with not only high specificity by means of viral targeting to cancer cells but also high efficacy by encoding immune modulators.

2  Virus manufacturing using a robust and scalable process

For the manufacturing of such a virus, a robust and scalable process is being developed, optimized by bioinformatic modeling. This process addresses the regulatory stipulations of Good Manufacturing Practice (GMP) to allow for a seamless transfer to GMP manufacturing.

3  Testing using novel and meaningful preclinical in vitro and in vivo models

For preclinical validation of the therapeutic viruses, a broad range of new models are being established to enable investigation of the therapeutic effects of these viruses on primary tumors and metastases in the presence of human immune cells. These include human 3D in vitro tumor models as well as complex humanized in vivo mouse models. 

As proof of concept, an oncolytic virus for treating non-small-cell lung cancer (NSCLC) is being developed.

The Fraunhofer-internal research project TheraVision is being coordinated by the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB. In addition, the Fraunhofer Institutes ITWM, ISC, IZI and ITEM are contributing their experience and know-how to the project. Since April 2017, Fraunhofer ITEM scientists in Braunschweig and Regensburg have been cooperating in this project.

The task of the researchers in Braunschweig in this project is to develop robust manufacturing processes for these novel therapeutics. Their starting point is a vector based on herpes simplex virus, which shall be developed further to enable targeted infection and killing of cancer cells in non-small-cell lung carcinoma and thus treatment of this type of cancer.

In Regensburg, Fraunhofer ITEM researchers collaborating in this project will develop novel preclinical cell models based on tumor samples from lung cancer patients. In addition, they will establish new in-vitro test systems that will enable drug testing in the presence of immune cells from the same patients. These test systems will then be used to investigate the capability of oncolytic viruses to kill tumor cells and activate the patient's immune system.