Mechanism: The science behind SonoTran

SonoTran® exploits a mechanical effect known as sustained inertial cavitation to actively pump therapeutic agents into and throughout solid tumours.

Inertial cavitation refers to the rapid expansion and subsequent collapse of bubbles under the effect of an ultrasound field. Sustained inertial cavitation results in the transfer of momentum from the bubbles into the surrounding medium.  This causes a net micro-streaming effect that can be used to propel therapeutic agents and other Sonosensitive Particles lying in the vicinity of the collapsing bubble.

OxSonics’ proprietary Sonosensitive Particles have been developed to carry pre-formed stabilised gas bubbles to enable sustained levels of inertial cavitation using low (quasi-diagnostic) ultrasound intensities at tumour sites. These particles are co-administered alongside unmodified (un-reformulated) solid tumour therapeutic agents. By virtue of their optimal size (400-500nm), the Sonosensitive Particles circulate in the blood stream, but can also “extravasate” (exit blood vessels) through the leaky endothelium of the vessels in solid tumours. Because the Sonosensitive Particles naturally re-stabilise gas on their surface following collapse, the process is repetitive through successive ultrasound pulses and this enables gradual active convection of the drug to distances of greater than 200 microns from blood vessels into tumours. 

These features combined have the potential to overcome two of the greatest limitations of solid tumour cancer therapy. In particular, cavitation-mediated microstreaming has been shown to enable accumulation of a greater proportion of the administered dose from the blood stream into the tumour; and improved penetration of the drug beyond the perivascular space to tumour cells lying as far as 150 microns from the nearest blood vessels.

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Evidence: Preclinical Data

SonoTran® has been shown to enhance the delivery of multiple oncology agents spanning multiple drug classes resulting in a significant enhancement of tumour retardation when compared to the oncology agents alone.

Example 1: Oncolytic Vaccinia Virus (Myers et al)

SonoTran® enhanced the delivery of an oncolytic vaccinia virus by a factor of 50-fold in a murine model (measuring luminescence of the reporter gene expression and corroborated by qPCR) one day post IV injection.  This 50-fold enhancement resulted in a 10,000-fold increase vaccinia virus activity by day six. Moreover, improved delivery resulted in significantly enhanced tumour retardation in four out of four animals in the SonoTran treatment group, compared to only one out of four animals in the control group.

 

 

Example 2: Checkpoint Inhibitor anti-PD-L1

SonoTran® has been shown to enhance the delivery of anti-PD-L1 in a preclinical murine model. Ten days after tumour implantation, the SonoTran Therapy Group received anti-PD-L1 (IV injection) together with SonoTran. Similarly the “Control Group” received anti-PD-L1 ten days after tumour implantation. Eighteen days following anti-PD-L1 administration, four out of five animals in the SonoTran Therapy Group exhibited significant tumour retardation versus the Control Group animals. By day twenty eight this culminated in four out of five animals surviving in the SonoTran Therapy Group compared with no survivors in the Control Group.

 

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publications
Publications

OxSonics’ core technology is based on more than a decade of research at the University of Oxford from within the Biomedical Ultrasonics, Biotherapy and Biopharmaceuticals Laboratory (BUBBL) at the Institute of Biomedical Engineering.

Key SonoTran™ Publications
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R. Myers, C. Coviello, P. Erbs, J. Foloppe, C. Rowe, J. Kwan, C. Crake, S. Finn, E. Jackson, J.-M. Balloul, C. Story, C. and R. Carlisle.
Polymeric Cups for Cavitation-mediated Delivery of Oncolytic Vaccinia Virus
Molecular Therapy (2016); 24 9, 1627–1633;
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J. Kwan, R. Myers, C. Coviello, S. Graham, A. Shah, E. Stride, R. Carlisle and C. C. Coussios
Ultrasound-Propelled Nanocups for Drug Delivery
Small; Volume 11, Issue 39 (2015) 5305–5314.  
Additional Peer-Reviewed Publications about Ultrasound-Enhanced Delivery to Tumours
Additional Peer-Reviewed Publications about Passive Acoustic Mapping
Additional Peer-Reviewed Publications about Sonosensitive Particles
Intellectual Property

OxSonics’ intellectual property consists of multiple patent families and a substantial body of know-how that are collectively designed to provide protection across both the SonoTran® Ultrasound System and the SonoTran® consumable Sonosensitive Particles. Patents protecting OxSonics® core technology have been granted across many key jurisdictions with several further patents at an advanced stage of prosecution.

 

 

© OxSonics Ltd 2017