Have you ever been to the Society of Toxicology (SOT) Annual Meeting? If you answered yes, you’ll know why we rank it as one of our 'must-attend' shows every year.
Over five busy and inspiring days, top toxicologists, thought leaders, and industry heavyweights from over 50 countries got together to share their research and expertise.
2019's SOT program packed in over 100 featured and scientific sessions. At these sessions, attendees discussed cutting-edge science, mechanisms and regulatory considerations - amongst many other hot topics.
The Envigo team were proud to host three sessions this year. Below you’ll find highlights from one of those sessions - Dr Kirsty Harper’s ‘Working with weird and wonderful viral vectors – how to combine animal husbandry and study design to ensure success’.
In her presentation, Kirsty examined how viral vectors fit into the bigger picture around the drug development process, particularly nonclinical safety assessment and study design. She explored how best to handle viral vectors, and how these insights can be used commercially to ensure you get your study design right first time, avoiding costly and time-consuming delays.
If you couldn’t make it to SOT 2019, you can still benefit from these practical insights. Kirsty will be presenting her SOT session in a live webinar on April 24.
Why viral vectors are becoming more popular
In her introduction, Kirsty described how and why viral vectors are being increasingly used in the following therapeutic settings:
- Gene therapies
- Viral vaccines
- Oncolytic viruses (viruses that selectively kill tumor cells)
She also explained how the use of a live viral product requires specific considerations, that are in addition to standard toxicology endpoints. This led to highlighting the goals of nonclinical safety assessment and what you should identify in your study design, and explained why working with viral vectors is different from traditional drugs.
Virally vectored products are complex and multi-factorial products with considerable potential for adverse affects. Each product will require its own ongoing assessments and evaluations during the study design and development process. “It’s very much a case-by-case approach”, Kirsty explained.
Specific viral vector considerations
Kirsty set out in detail the extra specific considerations for viral vectors and shared some advice on species selection, and the multiple factors you should consider to ensure your study design’s success.
The need to consider both the virus itself and any genes/antigens being delivered was highlighted, as well as a range of other questions you should ask yourself when developing these products:
- Can the virus infect the proposed toxicology species?
- Will the virus migrate to the same organs as in the clinic?
- Will the virus or its delivered gene/antigen be rapidly cleared by the immune system?
- Will the gene product be functional in the selected toxicology species? How will this present in an otherwise normal animal?
- Will the delivered antigen drive an appropriate immune response in the selected toxicology species? How will this be measured?
- Will any immune activating components be functional? Will they be immunogenic?
Kirsty described this as a scientifically challenging and potentially unpredictable area to navigate. Therefore, having the right strategy in place from the start is important. Getting it wrong, of course, means frustrating delays and extra financial costs which could potentially play havoc with your organization's budget, regulation submissions, and development milestones.
With these key commercial considerations in mind, Kirsty shared a practical and proven best-case situation for dealing with viral vectors.
Nonclinical safety assessment strategies
- Bioactivity and pharmacology profile
- Level of gene expression
- Extent of pharmacological 'correction'
When moving forward to your GLP studies, Kirsty stressed that it's important to “include appropriate PD endpoints to assess immune response and transgene function as appropriate”. She told attendees what they should expect when it came to their biodistribution studies. Likewise, she pointed out the target specificity issues they ought to be aware of.
The duration of toxicity studies was also an area of focus. Kirsty explained why the duration of the study would vary depending on the nature of the product, and which durations would be appropriate for individual situations.
Kirsty concluded her session by explaining a wide array of approaches with many different targets can lead to some interesting challenges and reminded her audience that rationally-designed mechanistic studies in relevant species are important in assessing safety.
Couldn't make this year's SOT? Join our April 24 live webinar instead.
In the same presentation made at SOT, Kirsty will be covering all the issues around viral vectors, animal husbandry and study design you read about above in our live webinar. Plus, you’ll have chance to take part in a Q&A with Kirsty herself. Secure your spot to 'Working with weird and wonderful viral vectors'.