Realizing the Potential of Oncolytic Viruses

Published: 3 March 2023

The oncology treatment space is advancing rapidly, with the number of clinical trials studying therapies targeting cancer indications up 56% from 2016 and a record 30 oncology novel active substances launched globally in 2021.[1] As the second leading cause of death worldwide, a drive to find new effective treatments has been responsible for this surge in oncology R&D activity.[2]

The traditional course of treatment for cancer has relied upon three different approaches, surgery, radiation, and chemotherapy. These treatment options have been successful in reducing the mortality rate of cancer by 32% from its peak in 1991 to 2019.[3] However, with research suggesting that the number of Europeans dying from cancer is set to increase by 34% between 2020 and 2040, there is still an urgent need to find novel cancer treatments.[4]

Next-generation therapies

In recent years, the drive for improvements in cancer therapy options led to a surge in the development of monoclonal antibodies (mAbs), with Merck’s Keytruda (pembrolizumab) representing the biggest selling oncology product, with full-year sales in 2021 of $17.2bn.[5] Antibody-drug conjugates (ADCs) also represent a growing part of the oncology pipeline, as a spate of recent approvals increases interest in the area. Other areas that are growing include chimeric antigen receptor (CAR) T treatments, due to their high levels of efficacy, and cancer vaccines or gene therapy approaches.

Central to the mode of action of these new generation cancer treatments is the ability to utilize the body’s immune system; they are therefore referred to as immuno-oncology treatments. Oncolytic viruses are a part of this new wave of treatments and there is much interest in it due to its ability to both leverage the immune system and their compatibility with other cancer treatments. As a result, between 2017 and 2020, the number of oncolytic treatments in the preclinical pipeline doubled, from 95 to 185.[6]

Meeting the potential of oncolytic viruses

When designed carefully, oncolytic viruses can recognize and selectively infect cancer cells, before then replicating within them. This approach allows oncolytic viruses to both directly destroy cancer cells and stimulate an anti-tumor response through the body’s own immune system. This latter attribute is enabled via the expression of specific markers that allow the immune system to recognize cancer cells that were previously undetected. They, therefore, hold enormous potential, both by themselves and when combined with traditional cancer treatments by improving their effectiveness.[7]

However, like all immuno-oncology treatments, OVs must be designed carefully to ensure they are both safe and effective – a task that requires considerable knowledge and expertise. The most important factors to consider when assessing an oncolytic virus are its selectivity, efficacy in lysis and immune stimulation, and safety.

It is crucial that oncolytic viruses are able to selectively target and lyse tumor cells whilst avoiding off-target toxicity, where healthy cells are mistakenly damaged. An ideal oncolytic virus would be able to recognize and target cancer stem cells and multiple tumor types.

Oncolytic viruses have the ability to generate a long-lasting, adaptive anti-tumor immune response – a critical characteristic for drug development to be successful. In this manner, metastases can also be targeted beyond the selective killing of tumor cells.

In terms of safety, they must be created to ensure genetic stability and prevent recombination that could result in wild-type (WT) virus particles that could be harmful to patients. They should also avoid genetic integration into the host genome and should not pose any risk to the germline. Though generating an immune response to cancer cells is desirable, triggering an auto-immune response specific to viral antigens is critical to avoid, as neutralizing the virus will impact efficacy.

Considerations in development and manufacturing

Once a safe and effective oncolytic virus candidate has been chosen, the development and manufacturing processes take on increasing importance. Depending on the targets of the virus and its purpose, different platforms will provide certain strengths and weaknesses. This is dependent on the viruses’ ability to be genetically modified, the way they reproduce within the cells, or their preferred target. There are a number of challenges that can surface in oncolytic virus production that need to be carefully managed. The key considerations are:

  • Cell lines: Cell lines already approved for development can be used to accelerate the upstream process. In terms of what cell line to select, this will depend on the type of oncolytic virus being developed, as well as other factors, such as whether the virus is enveloped or how productive the cell line is specifically for oncolytic viruses.
  • Cell and virus banks: Cell and virus seed materials can be used for the complete product lifecycle and are therefore crucial. Other considerations are the maximum density or virus titer, filling volumes, and the number of vials required. Storage will also need to be considered, such as whether further excipients are required to support oncolytic virus stability.
  • Development roadmap: The processes for oncolytic viruses have different requirements compared to other therapeutics, as drug substance (DS) and drug product (DP) development can be different. An example of this is virus recovery, which will vary depending on the product and the production system.
  • Analytical development: Quality control (QC) programs for OV products will test identity, potency, residuals, contaminants, safety, and relevant physicochemical parameters. Developers should pursue early regulatory advice to guarantee the testing panel proposed is the correct one.

Finding the right support

To address these considerations and all of the decisions along the development process for an OV, it is important to find a suitable partner. As the number of oncolytic viruses in the pipeline has increased, the demand for development and manufacturing capabilities and expertise is also accelerating. For those companies working on OVs, finding a specialist contract development and manufacturing organization (CDMO) will help to navigate the challenges that can occur and will aid in the decision-making process that is crucial in such a complex product.

To find out more about how Vibalogics could support the development and manufacturing of your next OV project, visit our oncolytic virus expertise page. Alternatively, you can contact the team here.

[6] ‘Immuno-Oncology Landscape’. Cancer Research Institute. [Accessed May 9 2022].
[7] Tian Y, Xie D, Yang L. Engineering strategies to enhance oncolytic viruses in cancer immunotherapy. Signal Transduct Target Ther. 2022 Apr 6;7(1):117.

We’re the ideal CDMO for your project

Get in touch