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Jill O'Donnell-Tormey: The Promise of Cancer Immunotherapy and Focused Ultrasound

Jill O'Donnell-Tormey, PhD, is chief executive officer and director of scientific affairs at the Cancer Research Institute. In 2017, CRI and the Focused Ultrasound Foundation partnered with the goal of advancing the development of new focused ultrasound and cancer immunotherapy treatments. A major part of the partnership is a joint fund that supports research to move toward new combination therapies. That fund awarded its first research grant in June of 2018. Dr. O’Donnell-Tormey appeared at the 6th International Symposium on Focused Ultrasound in October to discuss the partnership. Below is an edited transcript of our interview with her.

Why did you partner with Focused Ultrasound Foundation?
As immunotherapy was starting to gather momentum and there were more FDA approvals of immunotherapy, the Focused Ultrasound Foundation thought there might be a place to combine immunotherapy and focused ultrasound. So that was the impetus.

Strategically, it fits with the Cancer Research Institute’s view. We’ve been in this space for 65 years and feel that we have the world’s best scientific advisors when it comes to cancer immunology. Other organizations like the Focused Ultrasound Foundation don’t need to recreate the wheel but rather find ways to collaborate with us and build on the expertise we bring to this.

The future is in precision cancer immunotherapy, which means bringing the right combinations of various treatments or drugs together in the right patients.

I think it’s worth further exploration of what focused ultrasound actually does to a patient’s immune system. Is there a rational way to see how best to combine types of focused ultrasound with different cancers or with existing immunotherapy or experimental immunotherapies.

How do immunotherapy and focused ultrasound work together?
That’s the big question. I don’t know that we know that. That’s what our collaboration is intended to do in terms of jointly funding research to better understand that.

It’s not a simple answer because there are different types of focused ultrasound. They all seem to work in different ways. The Focused Ultrasound Foundation has been doing this research on its own to see if there is a standardized way to apply focused ultrasound and to understand what effect it has on the immune system, because focused ultrasound disrupts. It kills cells – and any killing of the cells could potentially release antigens that your immune system could see that could lead to the generation of an immune response against any cell that has those antigens.

So that was one thought – that certain types of focused ultrasound could be used to do that. But then there’s the impact on the immune response itself, which seems to cause release of different cytokines, and those could be positive or negative toward the activation of the immune response. There are still so many unanswered questions.

Combining these therapies sounds like a great hypothesis, but if you’re dealing with people who know focused ultrasound but don’t know the immune system, they could go down a path and say, “Let’s just combine this and see what happens.” Until you really understand the effects of focused ultrasound and then devise a rationale for how it could be combined with existing immunotherapies – or not – it doesn’t make sense to plow down the field of doing combination immunotherapy trials.

Instead, I think we can use a lot of the clinical trials that are ongoing with focused ultrasound. If we can somehow get access to the blood samples and have them looked at by people who know how to do immunological assays … that’s where I think the big opportunity is. Use what’s happening in the clinic already with focused ultrasound to come up with a rationale of how we could combine the two therapies.JillODT cropped 550

What’s the most exciting thing happening now with focused ultrasound and immunotherapy, something that’s closest to becoming a real treatment?
I think we’re a long way away from that. I’m very excited about the grant we’re working on together. We’re funding Gavin Dunn, MD, PhD, at Washington University in St. Louis, who is a neurosurgeon but also an immunologist. His colleague, Hong Chen, also does focused ultrasound. Together they can start dissecting perhaps what focused ultrasound is doing to the immune system.

It’s early days, but it’s those types of experiments and research that I think can get us some answers. I’m excited about that.

I’m also excited about the probability of places where focused ultrasound could be effective. Brain cancer seems to be a likely location. I also think pancreatic cancer is a good application, where there’s a lot of stroma, because we know focused ultrasound can disrupt stroma. That’s where it’s an unmet need, where immunotherapies haven’t yet proven to be a panacea or the big answer. But perhaps in combination with focused ultrasound they can be.

How close are we to the cure, to the moonshot?
I hate doing the crystal ball thing, but I think we’re making headway. Everyone is looking at a lot of different combinations. You’re dealing with a very complex system.

We will continue to see advances in the next 10-15 years, but I really do believe the future is personalized immunotherapy. There’s not going to be one size fits all. We’re learning the pieces. We’ve been very lucky with the checkpoint blockades – which have been a major breakthrough in immunotherapy – that they work as well as they do in a variety of cancers. And of course we’re not curing 100 percent of the patients. You’re getting 20-50 percent of patients responding, which is great.

To get the checkpoint blockades to work in greater numbers of cancer patients, we need research to understand what else is needed in a given patient to get an effective immune response, beyond just talking the brakes off the immune system.

If we can figure this out at the time of diagnosis we could develop the right cocktail of various treatments that would be expected to work in that given patient. We are years – if not decades – away from this, but that is the goal.

In the future, immunotherapy will be part of the collection of treatment options for all cancers, and focused ultrasound may well become one of the treatments that can be used in combination with it to deliver durable responses – if not cures – for more patients.

Additional Resources
Focused Ultrasound Foundation's Cancer Immunotherapy Program
Foundation Partners with Cancer Research Institute
Foundation Begins Working with the Parker Institute for Cancer Immunotherapy
Workshop Summary – Focused Ultrasound and Immunotherapy Summit (PDF)
Focused Ultrasound and Immunomodulation

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Jill O'Donnell-Tormey, PhD, is chief executive officer and director of scientific affairs at the Cancer Research Institute.