Theranostics 2020; 10(17):7925-7937. doi:10.7150/thno.44259

Research Paper

Engineering Circulating Tumor Cells as Novel Cancer Theranostics

Katie M Parkins1,2, Veronica P Dubois1,2, John J Kelly1, Yuanxin Chen1, Natasha N Knier1,2, Paula J Foster1,2, John A Ronald1,2,3✉

1. Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada.
2. The Department of Medical Biophysics, The University of Western Ontario, London, Ontario, Canada.
3. Lawson Health Research Institute, London, Ontario, Canada.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Parkins KM, Dubois VP, Kelly JJ, Chen Y, Knier NN, Foster PJ, Ronald JA. Engineering Circulating Tumor Cells as Novel Cancer Theranostics. Theranostics 2020; 10(17):7925-7937. doi:10.7150/thno.44259. Available from http://www.thno.org/v10p7925.htm

File import instruction

Abstract

New ways to target and treat metastatic disease are urgently needed. Tumor “self-homing” describes the recruitment of circulating tumor cells (CTCs) back to a previously excised primary tumor location, contributing to tumor recurrence, as well as their migration to established metastatic lesions. Recently, self-homing CTCs have been exploited as delivery vehicles for anti-cancer therapeutics in preclinical primary tumor models. However, the ability of CTCs to self-home and treat metastatic disease is largely unknown.

Methods: Here, we used bioluminescence imaging (BLI) to explore whether systemically administered CTCs home to metastatic lesions and if CTCs armed with both a reporter gene and a cytotoxic prodrug gene therapy can be used to visualize and treat metastatic disease.

Results: BLI performed over time revealed a remarkable ability of CTCs to home to and treat tumors throughout the body. Excitingly, metastatic tumor burden in mice that received therapeutic CTCs was lower compared to mice receiving control CTCs.

Conclusion: This study demonstrates the noteworthy ability of experimental CTCs to home to disseminated breast cancer lesions. Moreover, by incorporating a prodrug gene therapy system into our self-homing CTCs, we show exciting progress towards effective and targeted delivery of gene-based therapeutics to treat both primary and metastatic lesions.

Keywords: self-homing, CTC, self-targeted therapy, drug delivery, metastasis