Focused Ultrasound Surgery Foundation

The Departments of Radiation Oncology and Biomedical Engineering at the University of Virginia Health System launched a new FUS speakers’ series in January funded by the FUSF.

The first featured speaker was Chandan Guha, M.D., PhD, a world-class expert in tumor vaccines and director of Translational Research and Vice Chairman of the Department of Radiation Oncology at Montefiore Medical Center in Bronx, New York. His January 14 talk was entitled, “Ionizing radiation and ultrasound enhanced in situ tumor vaccines.”

Guha discussed results of some promising experiments in which he used both low and high intensity focused ultrasound (FUS) to stimulate different immunologic responses that could enhance cancer treatment. In particular, he found that focused ultrasound induced cellular protein unfolding and induced a cellular stress response, known as unfolded protein response.

By using nonablative, low energy FUS as a first step in his research, Guha hypothesized that he could induce protein unfolding and increase the expression of chaperone proteins – such as heat shock proteins (HSPs) – that try to repair protein misfolding. Overwhelming the immune system in this manner, he believed, would cause intratumoral misfolded proteins to be broken down by the proteosome and eventually increase the number of proteosome-processed, antigenic peptides that bind to HSPs.

As a second step, Guha exposed tumors to ablative, high energy FUS one to two days after using low intensity FUS. He believed this would induce cell death and cause the release of intra-tumoral peptide antigens into the extracellular compartment and into the blood stream, resulting in an autologous in-situ tumor vaccination.

Results, said Guha, indicate that sequential exposures of low and high FUS can stimulate the body’s own immune system to fight and eradicate cancer cells throughout the body.

Following Guha’s talk, James M. Larner, M.D., professor and chairman of UVA's Department of Radiation Oncology and director of the new FUS Center, offered the following statement:

“Dr. Guha has been the first to demonstrate that focused ultrasound treatment enhances antigen presentation to dendritic cells. His finding has significant clinical potential. Given that the University of Virginia has a strong peptide vaccine program led by Dr. Craig Slingluff, we are excited by the possibility of collaborations between Dr. Guha’s group and the University of Virginia, not only in the area of antigen presentation but also in several other areas as well. We are grateful to the Focused Ultrasound Foundation for allowing Dr. Guha to share his observations with leading FUS researchers at UVA and are optimistic about the possibilities of productive collaborations.”