Virotherapy is an emerging branch of therapies that explores viruses to defeat diverse types of diseases, including congenital genetic, infectious, cardiovascular and autoimmune diseases, especially cancers. Significant improvements in vector engineering, delivery, and safety have placed virotherapy at the forefront of modern medicine. So, it is important and necessary to perform preclinical data verification and project feasibility assessment in the development of a virotherapy project. As a leading CRO company with decades of industry experience, Creative Biolabs provides comprehensive preclinical & clinical assessment services to help reduce investment risk and accelerate the process of your project.
Mechanisms of Virotherapy
Generally, virotherapy works through three different pathways: gene overexpression, gene knockout, and suicide gene delivery.
Fig.1 The rationale of virotherapy.
Classification of Virotherapy
Oncolytic virotherapy is a therapeutic approach that utilizes native or genetically modified oncolytic viruses (OVs) to treat cancers. OVs promote anti-tumor responses through a dual mechanism of action: Directly by infecting and killing tumor cells and indirectly by stimulating a therapeutically relevant tumor-targeting immune response. OVs encompasses a broad diversity of DNA and RNA viruses with improved specificity and potency. Various OVs have been developed, including oncolytic measles virus, oncolytic vaccinia viruses, oncolytic HSV, reovirus and so on.
Applications of viral vectors have found an encouraging beginning in gene therapy due to virus tropism. Actually, particular viruses have been selected as gene delivery vehicles to carry foreign genes to specific tissues or cells to provide either transient or permanent transgene expression. The spectrum of viral vectors is very broad, including adenoviruses (Ads), retroviruses (γ-retroviruses and lentiviruses (LV)), poxviruses, adeno-associated viruses (AAVs), and herpes simplex viruses (HSV), etc. The choice of virus for clinical use depends on the efficiency of transgene expression, vector capacity, ease of production, safety, toxicity, and stability.
Viral immunotherapy utilizes genetically engineered viruses to present a specific antigen or immune modulator to the immune system to enhance the anti-tumor inflammatory response. The antigen may be derived from any species of virus/bacteria, or even cellular proteins released from the OV-lysed tumor cells, known as damage-associated molecular patterns and tumor-associated antigens (TAAs). These TAAs activate dendritic cells and elicit adaptive antitumor immunity.
Benefits of Virotherapy
There is a low probability for the generation of resistance;
Viruses usually replicate in a tumor-selective fashion and are non-pathogenic, only minimal systemic toxicity has been detected;
Virus dose in the tumor increases with time due to in situ virus amplification, as opposed to classical drug pharmacokinetics that decreases with time;
Viruses can be engineered to enhance safety and efficiency;
Directly infects tumor cells and its antitumor efficiency.
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