As a world-renowned service provider in the field of immunotherapy, Creative Biolabs offers not only a variety of optimized oncolytic virus products but also related engineering services, potency tests, safety, and toxicology analysis to our clients all over the world.
Oncolytic virus plays an increasingly important role in cancer immunotherapy with its favorable properties of direct cytotoxic activity on tumor cells, harmlessness to normal tissues, and induction of anti-tumor immune response. Actually, these engineered oncolytic viruses are also essentially recombinant viral vectors for gene therapy, which extensively include adenoviruses, herpes simplex viruses (HSV), vaccinia virus, vesicular stomatitis virus, measles virus, etc.
Since the first oncolytic virus, Oncorine (H101), was approved for the cancer treatment by the Chinese State Food and Drug Administration (CFDA) in 2005, oncolytic virus-based cancer immunotherapy has boomed in recent years. In addition to the widely used adenovirus, HSV is also one of the frequently utilized viruses in cancer therapeutic research. Talimogene laherparepvec (T-Vec) was an oncolytic HSV that was first approved for the melanoma treatment by the Food and Drug Administration (FDA) in October 2015, and then successively approved in Europe, Australia, Switzerland, and Israel.
Fig.1 Viral oncolysis mechanism of action and immunogenic response to viral infection. (Raman, 2019)
T-Vec is an attenuated HSV type I that is modified by two viral gene deletions and human granulocyte-macrophage colony-stimulating factor (GM-CSF) gene addition. The two viral gene deletions (γ34.5 and α47 genes) are designed for cancer-selective replication, attenuation of pathogenicity, and enhancement of the antitumor immune responses, while, GM-CSF gene insertion is intended for the increase of the accumulation and maturation of dendritic cells.
(i) Replication only in tumor cells: the deletion of the γ34.5 gene leads to the absence of infected cell protein 34.5 (ICP34.5), an important viral protein for infectivity by blocking the stress response of host cells. As the stress response in cancer cells is disrupted by themselves, T-Vec lacking ICP34.5 can replicate in tumor cells, but not in normal cells.
(ii) Enhanced antigen presentation: ICP47 encoded by the α47 gene is a viral protein responsible for virus’s escapement from the human immune response by inhibition antigen presentation. Thus, T-Vec lacking ICP47 enhances the level of antigen loading and presentation.
(iii) Enhanced anti-tumor immune response: GM-CSF is a human glycoprotein served as a cytokine promoting the accumulation and maturation of dendritic cells at tumor sites, further enhanced tumor antigen presentation, and priming T-cell response. So T-Vec with two copies of GM-CSF genes insertion triggers a systemic tumor-specific immune response.
Fig.2 Talimogene laherparepvec mechanism of action. (Raman, 2019)
Since the approval by the FDA in 2005, T-Vec has good tolerability and favorable antitumor effects in cancer treatment. Moreover, T-Vec-based combined immunotherapy has been widely researched for cancer treatment, among which T-Vec combined with ipilimumab and T-Vec combined with pembrolizumab have already proceeded into clinical trial stage.
Not only T-Vec but also a large number of oncolytic viruses being tested in clinical-stage are indicated to have a good therapeutic effect against cancer. Always dedicated to the improvement of human health, Creative Biolabs has successfully established a cutting-edge OncoVirapy™ platform aiming to provide our worldwide clients with the most diverse portfolio of oncolytic virus products and immunotherapy services.
If you’re interested in any oncolytic virus studies, please directly contact us for more information.
Please feel free to contact us for a quote and further discussion with our scientists.