There are few contract development and manufacturing organizations (CDMOs) capable of working with biopharmaceutical companies to develop advanced oncolytic virus (OV) therapies through to late-stage clinical trials and commercialization.
It is a highly specialized field requiring dedicated capacity, technology, and expertise. OV therapies present several unique challenges compared with other biopharma solutions that need to be addressed to produce an effective treatment that is safe for human use.
Explaining oncolytic viruses
OVs present an exciting and innovative new way to fight cancer. They are designed to infect, replicate, and kill cancer cells and cancer cells alone. This may lead to the presentation of both viral and tumor antigens in the patient, inducing innate and adaptive immune responses.
Such viral vectors are an ideal weapon against tumors because cancer cells have minimal antiviral defenses. As well as targeting cancer cells, OVs can be designed to deliver payloads, such as immunomodulating cytokines, which can trigger a long-lasting immune response in patients. The actual mechanisms of action for any given OV depend on the type of virus, how the virus is engineered, and the tumor itself.
Once the OV enters a cancer cell, it will replicate and cause the cancer cell to die. The cancer cell then lyses, releasing tumor antigens and other material which will provoke an immune response in the patient by activating dendritic cells. The direct lysis of the cancer cells, combined with the activation of the immune system, helps to enhance the impact of OVs in fighting cancer.
The challenge of oncolytic virus design
When it comes to OVs, the difficulty is to design a virus capable of replicating and spreading within a tumor as quickly as possible before they are attacked by the immune system. Work has been done over the years to develop OVs capable of evading the immune system for hours following a systemic injection to allow them to reach their target quickly.
Not only must OVs initially evade the immune system to be effective, but they also need to trigger an immune response to the cancer post-infection. The goal is to transform a “cold” tumor microenvironment lacking T cells into a “hot” environment that is inflamed and immunogenic.
Injecting OVs directly into a solid tumor is one effective way to maximize the infectivity potential of the tumor before clearance. However, several studies have discovered that intravenous injection of OV therapies in combination with immune checkpoint inhibitors can produce a much higher response rate than those using monotherapy. According to recent evidence, this can be achieved by combining OV therapy with immune checkpoint inhibitors that target mainly PD-1 and CTLA-4 protein receptor pathways.
OVs can also be loaded with other immunomodulators, like cytokines, to optimize and extend the immune response.
Finally, when designing a new OV treatment, it is important to select the most appropriate virus platform. The only OV currently approved for use is based on the herpes simplex virus (HSV-1), but several others are being researched in clinical trials. These include adenovirus, vaccinia virus, measles, coxsackie virus, vesicular stomatitis virus (VSV), reovirus, picornavirus (polio), Newcastle Disease Virus (NDV), and arenavirus.
The importance of working with development experts
Creating a new OV therapy is a complex business. Challenges must be overcome not just in discovery, but during the development and trial phase, then during the scaling and commercialization stage to bring it to market.
It is important for drug developers to have the support of a CDMO partner that has a rich pedigree in developing innovative OV treatments.
The right partner for the needs of a new OV project will not only offer reliable, high-quality viral vector support. They will also be highly flexible, open and communicative, always available to answer customer queries, provide regular updates on a project’s progress or propose solutions to unforeseen challenges. They will also be able to support at every stage of the development process, minimizing technical transfer delays to reduce time-to-market for new therapies.
These are the attributes that Vibalogics prides itself on possessing. For many years now, we have built a team of some sixty expert scientists, all focused primarily on process development, manufacturing, testing, and fill-finish of OV products in full compliance with international GMP standards in a GMO BSL-2 classified facility in Germany.
Vibalogics is now in the final stages of developing a facility that will be capable of manufacturing new late-stage and commercial products near Boston, Massachusetts. When the facility is operational later this year, it will enable us to provide an end-to-end development and manufacturing service for new OV therapies, helping us to further streamline project delivery for customers.
The perfect partner is the real secret to success
Finding the right CDMO partner is the real secret to successful OV development. By working with viral vector experts, biopharmaceutical companies can be confident that they will have the support they need to develop their OV discovery and bring it to clinical trial and beyond, to commercialization and production post-approval.