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Virotherapy Research in Germany: From Engineering to Translation
Guy Ungerechts1,2,3, Christine E Engeland1,2, Christian J Buchholz4,5
11 Department of Medical Oncology, National Center for Tumor Diseases and Heidelberg University Hospital , Heidelberg, Germany .
Abstract:
Virotherapy is a unique modality for the treatment of cancer with oncolytic viruses (OVs) that selectively infect and lyse tumor cells, spread within tumors, and activate anti-tumor immunity. Various viruses are being developed as OVs preclinically and clinically, several of them engineered to encode therapeutic proteins for tumor-targeted gene therapy. Scientists and clinicians in German academia have made significant contributions to OV research and development, which are highlighted in this review paper. Innovative strategies for "shielding," entry or postentry targeting, and "arming" of OVs have been established, focusing on adenovirus, measles virus, parvovirus, and vaccinia virus platforms. Thereby, new-generation virotherapeutics have been derived. Moreover, immunotherapeutic properties of OVs and combination therapies with pharmacotherapy, radiotherapy, and especially immunotherapy have been investigated and optimized. German investigators are increasingly assessing their OV innovations in investigator-initiated and sponsored clinical trials. As a prototype, parvovirus has been tested as an OV from preclinical proof-of-concept up to first-in-human clinical studies. The approval of the first OV in the Western world, T-VEC (Imlygic), has further spurred the involvement of investigators in Germany in international multicenter studies. With the encouraging developments in funding, commercialization, and regulatory procedures, more German engineering will be translated into OV clinical trials in the near future.
Insights
German scientists are advancing cancer treatment with oncolytic viruses (OVs). These engineered viruses selectively target tumors, activate immunity, and are progressing through clinical trials, showing great promise for future therapies.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Virotherapy utilizes oncolytic viruses (OVs) to selectively infect and destroy cancer cells, stimulate anti-tumor immune responses, and spread within tumors.
- OVs are engineered to deliver therapeutic proteins for targeted gene therapy, with significant advancements made by German academic researchers.
- Platforms like adenovirus, measles virus, parvovirus, and vaccinia virus are being developed and refined for enhanced efficacy.
Purpose of the Study:
- To review the significant contributions of German academia to oncolytic virus (OV) research and development.
- To highlight innovative strategies in OV engineering, including shielding, targeting, and arming.
- To discuss the progress of OV-based therapies in preclinical and clinical settings, with a focus on German contributions.
Main Methods:
- Review of preclinical and clinical research on oncolytic viruses (OVs) conducted by German scientists.
- Analysis of innovative strategies for engineering OVs, such as "shielding," entry/postentry targeting, and "arming."
- Examination of combination therapies involving OVs with immunotherapy, pharmacotherapy, and radiotherapy.
Main Results:
- Development of new-generation virotherapeutics based on adenovirus, measles virus, parvovirus, and vaccinia virus platforms.
- Investigation and optimization of OV immunotherapeutic properties and combination therapies.
- Increasing assessment of OV innovations in German investigator-initiated and sponsored clinical trials, including parvovirus as a prototype.
Conclusions:
- German investigators are actively translating OV innovations into clinical trials, spurred by regulatory advancements and the approval of T-VEC (Imlygic).
- Parvovirus has shown promise as an OV, progressing from preclinical studies to first-in-human trials.
- Future developments in funding, commercialization, and regulatory pathways are expected to accelerate the clinical translation of German OV research.
