Shining a Light on the Immune System to Inform Medicine Development at GSK
Dr Catherine Hines, Executive Director and Head, Clinical Imaging, leads and supports the imaging strategy for GSK trials. She tells us how imaging is helping us to understand the immune system, and what imaging is elucidating for medicine development.
What work are you leading in clinical imaging at GSK?
My group in Precision Medicine handles all of the radiological imaging endpoints on GSK trials, and sets the imaging strategy alongside our Oncology Clinical Development colleagues, to match any sort of unmet needs for an asset. This includes which RECiST criteria, identifying the risk in the disease or asset, etc. and then we execute the strategy and ensure data quality.
Imaging has great utility in determining the fate of things that are traditionally very hard to model, and answer questions that can otherwise not be solved. Particularly as drug development gets more complex, there are drugs – like a bispecific, trispecific or ADC payload – that affect the PK or biodistribution, which we can’t always easily model. For those, imaging can help solve those challenges.
What advances in imaging are enabling IO progress?
I’m a firm believer in immunoPET, which involves radiolabeling an antibody and determining biodistribution or exposure, for example.. We are looking to understand whether there are any sinks or if antibodies pool in unexpected places, which could then have a potential toxicology risk, for example. This research doesn’t affect clinical practice, but it can help us with internal clinical decision-making to better understand our medicines.
In addition, I’ll call out radiomics, and how it is helping to advance our understanding of response prediction, who the right patient population is, what those phenotypes are, etc. Those approaches can be used to enroll, enrich or balance studies, for example. Radiomics may help to identify features of patients that will respond and then someday assist with approval of drugs in those targeted populations.
"Particularly as drug development gets more complex, there are drugs that affect the PK or biodistribution, which we can’t always easily model. For those, imaging can help solve those challenges."
What are your short-term and long-term expectations for imaging’s impact on our work in IO?
In the short term, it's more centered on enrollment strategies. Hypothetically, we can understand from X score that a patient has a certain percent chance of responding to treatment. We may someday be able to use these findings to balance populations against placebo to avoid a false negative.
In the long term – five-plus years – I can’t think of any imaging person who wouldn’t want an imaging companion diagnostic. That is something I would love to see happen.
How are advances in our understanding of cancer impacting imaging, or vice versa?
Imaging informs the disease. A great non-oncology example of this is neurodegeneration. In neurodegeneration, there is the ATN classification system, which tells you if you’re amyloid beta positive or negative (measured with PET), tau positive or negative (measured with PET), and then neurodegeneration (measured with MRI). Imaging helps us understand how these patterns progress with disease intensity.
When we look at oncology, we are better able to define disease heterogeneity, not just via imaging but also biologically. What we understand about the staging of disease also informs imaging, and thus patient outcomes. We can tell you if a therapy worked or not, and feed back those results to ask, “Why did this patient respond or not respond?” and that informs biology. When you can monitor a disease, you learn more about the mechanisms of actions, phenotypes, etc.
What are the questions in immuno-oncology you want imaging to help answer?
I've been very interested in the role of fibrosis in oncology. If you read some of the literature in this space, we are discovering through single-cell sequencing and spatial transcriptomics the role of the fibroblast and the various cytokines that it produces to keep T cells at bay, for example, and to be immune exclusionary.
Can we use immunoPET to interrogate, for example, if T cells got into the tumor microenvironment or if our antibodies made it past the stroma?
"When you can monitor a disease, you learn more about the mechanisms of actions, phenotypes, etc."
What drew you to a career focus in imaging?
I did my undergrad in biochemistry, but I wasn’t passionate about it for my career. . I wanted to do something more applications-focused. I had done internships in NMR (nuclear magnetic resonance), worked in a veterinary lab, and I loved physical chemistry.
During my time in a veterinary lab, we were studying biomechanics, and I realized biomedical engineering had an imaging component. It was a lightbulb moment, because it was at the nexus of multiple interests – engineering, veterinary, NMR, and application-focused. And being in pharma makes me feel like I’m providing impact.
What advice would you give young people entering careers in science?
I had the luxury to try various tasks and functions: NMR, veterinary medicine, stem cell research, etc. That allowed me to figure out what I liked the most., so this would be my advice: try on various opportunities and find out what you like best, because you will be very good at something you enjoy doing.
And in a corollary to that, I’m glad that I said yes to new opportunities so that those doors didn’t close early on. If I had not said yes to certain opportunities, I may not have gone as far because I wouldn't have had the exposure and the working knowledge in a lot of different areas.
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