Assessment of the effect of oncolytic virotherapy in combination with cavitational ultrasound in the treatment of colorectal liver metastases using a precision cut tumour slice model


Year:

Session type:

Theme:

Marcos Kostalas1,Joshua Owen2,Claudia Hill2,Christopher Smith3,Nicola Annels3,Robert Carlisle2,Hardev Pandha3
1Royal Surrey County Hospital, Guildford, UK,2University of Oxford, Oxford, UK,3University of Surrey, Guildford, UK

Abstract

Background

Oncolytic virotherapy is a powerful emerging tool in the treatment of cancer. Clinical trials have confirmed the therapeutic effects of oncolytic virotherapy in the treatment of multiple solid tumours. A limitation of this novel treatment is the restricted ability of oncolytic viruses to reach and to penetrate target tumours following intravenous administration. One proposed method of overcoming this is through the concurrent application of ultrasound and specialised cavitational nuclei that expand and violently collapse at specific frequencies enabling greater tissue penetration of anti-cancer agents.

Method

Tissue cores, up to 8mm in diameter were obtained from patients with colorectal liver metastases. Cores were sliced using a vibrating microtome to 300┬Ám thickness. These were then treated with oncolytic vaccinia virus. Ultrasonic exposures were carried out using the System for Acoustic Transfection (SAT) chamber. This system was based on prior design but modified to allow a decrease in the exposure area for the prepared tumour slices.

Results

Initial experiments found that vaccinia virus in combination with cavitational ultrasound and sulphur hexafluoride microbubbles significantly increased staining for cleaved caspase 3 in treated organotypic cultures of colorectal liver meatsatases compared with vaccinia virus alone. The study also found that the combination of oncolytic virus treatment and cavitational ultrasound enabled the utilisation of lower viral concentrations whilst maintaining similar levels of staining for cleaved caspase 3 and therefore virus activity compared with higher concentrations of virus.

Conclusion

Overall, we found that the combined treatment of colorectal liver metastases with vaccinia virus and exposure to cavitational ultrasound and sulphur hexafluoride microbubbles improved the anti-cancer effects of oncolytic vaccinia virus. Combining this treatment with oncolytic virotherapy is a promising technique to improve the anti-cancer effect following the systemic administration of oncolytic vaccinia virus.