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SUMMARY:Shaken and Stirred: Ultrasound-Enhanced Drug Delivery and Immuno-O
 ncology - Professor Constantin-C. Coussios - Statutory Chair of Biomedical
  Engineering\, University of Oxford
DTSTART:20191210T110000Z
DTEND:20191210T120000Z
UID:TALK133621@talks.cam.ac.uk
CONTACT:Kirsty Shepherd
DESCRIPTION:Tumour physiology presents a formidable barrier to the deliver
 y of current and emerging anticancer therapeutics\, including small-molecu
 le-containing nanomedicines\, oncolytic viruses\, and therapeutic antibodi
 es. The thermal and mechanical effects produced by ultrasound have a major
  role to play in enabling therapeutics to overcome the elevated intratumou
 ral pressure\, sparse vascularity and dense extracellular matrix encounter
 ed in the majority of solid tumours\, in order to achieve better intratumo
 ural distribution and therapeutic efficacy. \nWe will start with a brief p
 resentation of the results and lessons learned from the first-in-man trial
  of remotely activated oncological drug delivery (TarDox\, Lancet Oncology
  2018)\, which exploited the thermal effects of extracorporeal ultrasound 
 in order to trigger the release of a small molecule from thermosensitive l
 iposomes. The 10-patient Phase I study demonstrated a significant enhancem
 ent (3.7-fold) in the intratumoural dose of doxorubicin in liver tumours f
 ollowing ultrasound for the same systemic dose of the drug\, with subseque
 nt radiological response observed in several tumour types that do not typi
 cally respond to doxorubicin. \nWe will then present a novel technique exp
 loiting a mechanical effect of ultrasound\, known as acoustic cavitation\,
  to enable convective transport and delivery of therapeutics in solid tumo
 urs. This approach presents the additional benefit of not requiring modifi
 cation or encapsulation of the drug and the use of lower-intensity ultraso
 und delivered from a portable device. Sub-micron cavitation-inducing parti
 cles co-administered with oncolytic viruses\, antibody-drug conjugates or 
 checkpoint inhibitors (aPDL1\, aPD1) have been shown to increase both the 
 penetration and total dose delivered to tumours\, and to significantly enh
 ance the therapeutic efficacy of these emerging therapeutics even at a red
 uced systemic dose. Most recently\, we found that the combination of drug 
 and cavitation was critical in producing sustained innate and adaptive imm
 une responses. \n\n
LOCATION:Electrical Engineering\, Department of Engineering - EED Seminar 
 Room - 9 JJ Thomson Avenue\, Cambridge\, CB3 0FA
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