Dr. Ferrara’s presentation, “Recent developments in molecular imaging and focal therapy using ultrasound,” described new frontiers in therapeutic ultrasound and ultrasound imaging of cancer and how the synergy between focused ultrasound and immuno-oncology is progressing. It also included studies from her group that demonstrate that a combination focal ablation ultrasound therapy with agonists creates a T-cell response that leads to enhanced immunotherapy outcomes.
Frédéric Padilla, PhD, the Foundation’s Director of Applied Physics Research, presented preclinical cancer immunotherapy research that was conducted at LabTAU, a focused ultrasound Center of Excellence. The team’s abstract, “Effect of a combined immune checkpoint inhibitor and mechanical focused ultrasound treatment on intratumoral immune response in a MC38 preclinical model,” described a study combining the mechanical effects of focused ultrasound with an immune checkpoint inhibitor in a model of colon cancer.
“Our combination treatment showed promise for controlling tumor growth and prolonging survival in this model,” said Dr. Padilla. “The data show that this enhanced response is immune dependent, certainly through a CD8-mediated response, and we think that the immune infiltrate changes led to the transient effect that we observed.”
Additional studies were presented from researchers at Sunnybrook Research Institute, the National Institutes of Health (NIH), and a collaboration between the University of Chicago and the New Mexico Institute of Mining and Technology.
NIH research teams presented posters on using pulsed focused ultrasound to modulate immune responses in preclinical breast cancer and melanoma models. The Sunnybrook team presented a poster describing how the combined use of focused ultrasound and microbubbles can enhance the effects of a clinically relevant combination anti-PD-L1 plus paclitaxel (PTX) in a preclinical model of triple negative breast cancer. The Chicago team evaluated a novel liposomal formulation of topotecan, an agent used for treating neuroblastomas. The novel formulation was tested in vitro, and the data suggest that liposomal encapsulation does not inhibit topotecan release, but could increase its tumoral cytotoxicity by increasing its half-life, therefore allowing focused ultrasound and microbubbles to increase its uptake in xenografts.
Focused Ultrasound Content
ED22 Molecular Imaging in Cancer Research
Recent developments in molecular imaging and focal therapy using ultrasound
Katherine W. Ferrara. Stanford University, Palo Alto, CA
LB-078/5 - Effect of a combined immune checkpoint inhibitor and mechanical focused ultrasound treatment on intratumoral immune response in a MC38 preclinical model
Cécile Fant, Chloé Grasselly, Morgane Denis, Doriane Mathé, Pierre-Antoine Choffour, Loic Daunizeau, Jean-Louis Mestas, Cyril Lafon, Christophe Caux, Stéphane Depil, Charles Dumontet, Frédéric Padilla. LabTAU U1032, Lyon, France, Antineo, Lyon, France, CRCL INSERM U1052, Lyon, France, Anticancer Antibodies, CRCL,
INSERM U1052, Lyon, France, FUS Foundation, Charlottesville, VA
LB-079/6 - Microbubble mediated focused ultrasound therapy enhances the antitumor potency and durability of anti-PD-L1 checkpoint blockade
David Goertz, William Cruz, Sharshi Bulner, Alex Wright, Robert Kerbel. Sunnybrook Research Institute, Toronto, ON, Canada
1729 - Novel liposomal topotecan formulation has a lower IC50 than the free form on neuroblastoma cells
Paula Viza Gomes, Stephanie Shen, Meghan Hill, Kilkee Flynn, Mendi Marquez, Liliya Frolova, Jessica J. Kandel, Michaelann Tartis, Sonia L. Hernandez. University of Chicago, Chicago, IL, New Mexico Institute of Mining and Technology, Socorro, NM
2665 - Immune cell modulation of pulsed focused ultrasound in murine melanoma and breast cancer models
Parwathy Chandran, Gadi Cohen, Scott R. Burks, Joseph A. Frank. National Institutes of Health, Bethesda, MD
3577 - Pulsed focused ultrasound induces cytosolic calcium transients that increase free radical production and dsDNA breaks in tumor cells
Robert B. Rosenblatt, Joseph A. Frank, Scott R. Burks. NIH Clinical Center, MD
5606 - Characterization of temporal proteomic dynamics of murine breast and melanoma tumor microenvironments without and with pulsed focused ultrasound
Gadi Cohen, Parwathay Chandran, Lauren E. Tomlinson, Maggie E. Sundby, Rebecca M. Lorsung, Scott R. Burks, Joseph A. Frank. NIH Clinical Center, Bethesda, MD