Immunotherapy Study Launched Under New Guidelines
- Multisite focused ultrasound studies present logistical challenges.
- The Foundation’s newly released guidelines help organizations more effectively plan and execute these projects.
- An upcoming study of focused ultrasound and immunotherapy in a pancreatic cancer model is employing these guidelines.
After the September 2021 Focused Ultrasound and Cancer Immunotherapy workshop, many questions remained unanswered about the immune effects of the various modes of focused ultrasound and whether the effects varied by tumor type. The research community was enthusiastic about planning a study to compare multiple modes of focused ultrasound across several tumor types but hesitant about the best approach.
Multimodal focused ultrasound studies are inherently complicated. Few research laboratories have extensive experience with more than one focused ultrasound modality, because each requires specialized equipment. Therefore, multimodal studies often necessitate the involvement and coordination between several institutions. While multisite projects always present logistical challenges, immunotherapy projects produce additional hurdles due to the sensitivity of the research. For example, differences in the gut microbiome of the mice, which can occur if mice are bought from different vendors or housed in different vivaria, can impact the results. Cancer cell lines must be the same age, fed the same media, and handled the same way. Some experimental samples can be sent off for blinded third party analysis while others must be processed right away on equipment that varies from site to site. Harmonizing protocols and data to obtain statistically meaningful results is no easy feat.
To address some of these challenges, the Foundation developed new guidelines (adapted from a framework produced by the Health Research Alliance) to facilitate dialogue and aid in planning around the areas that are critical to effective team science. The guidelines seek to foster efficient research and prevent some of the difficulties involved in large multisite projects. They also encourage upfront discussion of labor distribution and expectations of each party. Collaborators are asked to consider potentially divisive topics, such as publication authorship, and establish procedures for settling any disagreements.
The Foundation is releasing these guidelines as a useful resource for the focused ultrasound research community, especially as the field continues to grow and projects become larger and more complex. We encourage researchers to consult and apply these guidelines when planning preclinical and clinical studies. The Foundation strongly recommends that these guidelines be used in studies that we are evaluating for funding support.
“The Foundation has always encouraged collaboration within our field, but we recognize that collaborative research projects create unique challenges,” said the Foundation’s Chief Scientific Officer, Jessica Foley, PhD. “We hope that these guidelines can help researchers make choices early in their collaborative process that best set them up for success.”
As a first test of the multisite collaboration guidelines, the Foundation funded a study titled “Multimodal analysis of immune response post-FUS in two tumor models.” The goal is to compare the immune effects of thermal ablation, boiling histotripsy, and cavitational histotripsy in a pancreatic cancer model. If initial experiments go well, a melanoma model will be added. The research teams are led by Dr. Zhen Xu at the University of Michigan, Dr. Tatiana Khokhlova at the University of Washington, Drs. Brett Fite and Katherine Ferrara at Stanford University, and Dr. Frederic Padilla at the Focused Ultrasound Foundation. Each group is devoting significant effort to developing experimental and analytical protocols that could be standardized across all three laboratories. The project includes numerous controls to isolate treatment effects from experimental “noise,” and the group will hold monthly meetings to ensure that the project remains on track.
Designed to answer fundamental questions about how focused ultrasound interacts with the immune system in the cancer setting, this project is the culmination of years of effort from the Foundation, the focused ultrasound immunotherapy research community, and the team of scientists dedicated to its success.
“I am excited by this opportunity to compare focused ultrasound parameters in a model of aggressive pancreatic cancer,” said Dr. Fite. “I believe this study will improve our understanding of the technology’s immunological effects, allowing us to develop improved therapies and rapidly translate them to patients.”