In a white paper for IDT Biologika Dr Heidi Trusheim and Trevor Broadt examine the process of developing oncolytic viruses and how to avoid problems. Oncolytic viruses (OVs) have the “potential to revolutionise standard cancer treatment”. Researchers continue to “pursue the optimisation of these viruses” through engineering strategies, but Dr Trusheim and Broadt suggest that progress relies on the achievement of several goals. These are related to “safety, efficacy, and commercial scale-up”. The first oncolytic to receive FDA approval was in 2015, and since then the “need for contract development and manufacturing organisation (CDMOs) with experience in viral vector design” has become more pressing.
How to avoid the “pitfalls of oncolytic virus design”
OVs are so exciting to the industry because they have two “primary modes of action”:
- They can kill infected cancer cells
- They can stimulate cross-primes cancer immunity to “boost the killing of uninfected cancer cells”.
Thus, they offer great improvement potential to current cancer therapies. Recent research focuses on equipping OVs with a range of transgenes to “increase their immune stimulation, modulate immune checkpoints, and provide imaging targets”. The basic science at the “core” of OV immunotherapy is over a century old. However, more recently it has been applied to a range of engineered viruses. Unfortunately, limited development capabilities mean that “only a few adenovirus-based oncolytic therapies have been approved by regulators”. Despite this developmental drawback, many are in development or at clinical trial stage.
One of the key reasons for the slow development is the need to ensure the “relative safety of the viral vector”. The “foremost consideration” for early clinical trials is “minimising the potential for viral replication in health cells”.
Another “variable” is preventing the non-retroviral OVs from “integrating into the host’s genome”. The chance of “random recombination” is another factor to be tested. Dr Trusheim and Broadt emphasise the importance of research into the transgene incorporated in viral vectors, to “eliminate the potential for homologous sequence recombination”.
“reducing or eliminating the potential for unforeseen scenarios often comes down to fundamentals”
Partnering for expertise at all levels
Dr Trusheim and Broadt insist that “vetting” a partner “comes down to the basics”. Unless this process is thorough, the scale-up can be delayed. They suggest identifying a manufacturing partner with a “proven track record” or design and manufacturing. Furthermore, partners should understand the “primary challenges that plague oncolytic virus design”.
“Because only a handful of oncolytic viral therapies exist on the market today, the regulatory environment surrounding them is still relatively fluid.”
Partners should have experience in “engaging with regulators” and “interpreting regulatory guidance”. IDT Biologika, for example, has a “well-codified” approach to scale-up. End-to-end development is enhanced by tailored facilities and equipment. So far in the past year IDT Biologika has successfully supported the development of viral vector applications including pox viruses, adenoviruses, and measles virus.
“IDT’s experience in optimising not just the cell line and passage range, but the media and viral harvest conditions, offers customers the latitude to pursue these under-explored, highly transformative therapies with more confidence.”
To hear from IDT Biologika’s Senior Vice President of Development, Dr Simone Kardinahl, at the World Vaccine Congress in Europe 2022 click here for tickets.
For the full paper by Dr Trusheim and Broadt, click here to download a copy.