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Carson-Zagzebski Distinguished Lectureship On Medical Ultrasound

K Ferrara1*, (1) Stanford University, Stanford, CA


(Tuesday, 7/16/2019) 11:00 AM - 12:15 PM

Room: 303

Therapeutic ultrasound has long been recognized for the ability to directly treat disease through mechanical and thermal effects. More recently, opportunities to synergize with immunotherapy and gene therapy are emerging. In situ cancer vaccination represents an alternative strategy for cancer immunotherapy that combines stimulants and antigen release at a treatment site to enhance the innate immune system and exploit the tumor-associated antigens. Our work has shown that there are 4 mechanisms by which focal ablation synergizes with immunotherapy to create in situ vaccination: 1) all tumor cells within a defined region of interest can be killed, 2) therapeutic penetration and accumulation is enhanced (e.g. drug accumulation up to 25%ID/cc and 50-fold), 3) tumor specific antigen is presented on macrophages and dendritic cells in tumor and lymph nodes at higher levels than achievable by either treatment alone and 4) dying tumor cells release cytokines inducing a viral-like anti-tumor response. We find that immune adjuvants, combined with focal ablation, can result in a complete response in multi-site cancers in mice and will explore the translational possibilities.

Microbubble-based transfection also has the potential to treat disease in new ways. The expansion of circulating microbubbles is constrained; yet, wideband echoes can be created, and effective imaging protocols have been developed. This same microbubble oscillation can enhance vascular and cell membrane permeability facilitating the introduction of nucleic acids. We have recently performed a series of studies of ultrasound-mediated transfection and will describe the potential development and applications of this work.

Learning Objectives:
1. To understand the mechanisms of therapeutic ultrasound to enhance drug and gene therapy.
2. To understand the synergies of therapeutic ultrasound with treatment approaches such as immune adjuvants and nucleic acids.
3. To understand the potential applications of therapeutic ultrasound.



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