Dr. Craig Slingluff is a University of Virginia Professor of Surgery who is conducting a clinical trial to study the effects of focused ultrasound with or without a cancer immunotherapy drug (pembrolizumab or imiquimod) to treat advanced solid tumors.
We recently asked him about his interest in combining focused ultrasound with immunotherapy and his ideas for future studies.
Focused Ultrasound Work
When and how did you become interested in focused ultrasound?
Over the past few years, I became interested in focused ultrasound because of the exciting research being done with it by my colleagues at the University of Virginia (UVA). I have been impressed with the development of focused ultrasound ablation (FUSA) for sites in the brain that cause tremor. In fact, one of my patients with melanoma was on the initial trial of FUSA for tremor, and his benefit was dramatic.
I have had many professional discussions and planning meetings with Dr. Richard Price and Dr. Tim Bullock and have co-mentored Natasha Sheybani, an exceptional PhD student working with Dr. Price on the role of focused ultrasound in breast cancer and brain tumors, both for drug delivery and for enhancing immune-mediated tumor control.
I have also collaborated with Dr. Kumari Andarewewa and have learned from her and from her colleagues, including Dr. Wilson Miller.
I have also closely followed the work of my colleague Dr. David Brenin in his clinical application of focused ultrasound to treat benign and malignant breast tumors. I applied for an internal grant to support a clinical trial of partial FUSA of melanoma and other cancers, and that trial (AM003), is now open and enrolling patients.
What are your areas of interest in focused ultrasound?
I am primarily interested in its promise and applications for the treatment of cancer, by its direct effects by its enhancement of anti-tumor immune responses, or by enhancing therapeutic drug delivery.
What mechanisms and clinical indications do you study?
My main focus is on advanced melanoma, but the AM003 trial is also open to patients with a wide range of cancers that have not responded to other treatments.
What is the goal of your work?
My most direct involvement in focused ultrasound research is as one of the leaders of the AM003 clinical trial, “Pilot Evaluation of Focused Ultrasound Ablation and Focused Ultrasound Ablation Plus PD-1 Antibody Blockade in Advanced Solid Tumors,” My colleague Lynn Dengel, MD, is the study's principal investigator, and Rachita Khot, MD, is a key co-investigator. We are studying the safety of partial FUSA of solid tumors and the ability of partial FUSA to increase infiltration of immune system cells into the treated cancers and to induce regressions of advanced cancers.
What are your funding sources?
The AM003 clinical trial is jointly funded by the UVA Department of Radiology and Medical Imaging and the Focused Ultrasound Foundation. It is an approved project within the ongoing collaboration between UVA and the Foundation at the UVA Focused Ultrasound Center of Excellence.
I also collaborate with Kumari Andarewewa, PhD, on her recent Department of Defense (DoD) grant to study focused ultrasound in breast cancer in preclinical models. For other research, I have funding from the DoD, the Cancer Research Institute, and the National Cancer Institute, as well as philanthropy and corporate partners.
Who are your team members?
My team includes Lynn Dengel, MD (surgery); Rachita Khot, MD (radiology); Kathleen Haden, NP (surgery); Rachael Reed, Clinical Research Coordinator (cancer center); Kim Bullock, PhD (protocol writer, cancer center); and Meagan Darling (regulatory staff).
Who are your collaborators?
My other clinical collaborators are David Brenin, MD (breast surgeon), and Patrick Dillon, MD (medical oncology).
What are your greatest achievements?
In the area of focused ultrasound clinical research, the achievements of our team include navigating the challenges of the US Food and Drug Administration (FDA) in gaining approval for the AM003 clinical trial to use focused ultrasound therapy in many different body sites for which no prior approval existed.
What do you see as impediments to your success?
This clinical trial depends on technical support from the company that makes the focused ultrasound device (Theraclion). Theraclion is based in France, so our initial patients required that one of their scientists travel to the US to support the treatment.
However, Theraclion has been very supportive, and we have already enrolled two patients with their help. More recently, our team has developed methods for remote communication to continue and to schedule these treatments without requiring a Theraclion scientist to travel here.
What is on your research wish list?
We are working on a new research proposal to test positron emission tomography (PET) imaging with an antibody to CD8 T lymphocytes. We would like to investigate whether focused ultrasound therapy enhances CD8 T cell infiltrates in treated and untreated tumors. This is a team effort involving Dr. Lale Kostakoglu and Dr. Lynn Dengel.
Has the Foundation played a role in your work?
Yes, the Focused Ultrasound Foundation has had a major role in the University receiving funds to support the AM003 clinical trial as well as other research on focused ultrasound therapies.
How many patients have you treated?
To date, we have treated two patients in the AM003 clinical trial.
What can you tell us about the patients who have been enrolled in the trial?
Both patients were those with advanced cancers who had no other meaningful treatment options. The AM003 trial gave hope to both patients and their families. More stories will arise as we treat more patients.
Will you have any follow-up funding opportunities?
There are many, but first we will work on completing the AM003 trial.
What comes next?
The PET imaging trial to evaluate infiltration by CD8+ immune cells, as mentioned above.
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