Optical detection and virotherapy of live metastatic tumor cells in body fluids with vaccinia strains

PLoS One. 2013 Sep 3;8(9):e71105. doi: 10.1371/journal.pone.0071105. eCollection 2013.

Abstract

Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response. Here we report, for the first time, that live metastatic tumor cells in blood samples from mice bearing human tumor xenografts and in blood and cerebrospinal fluid samples from patients with cancer were successfully detected using a tumor cell-specific recombinant vaccinia virus (VACV). In contrast to the FDA-approved CellSearch system, VACV detects circulating tumor cells (CTCs) in a cancer biomarker-independent manner, thus, free of any bias related to the use of antibodies, and can be potentially a universal system for detection of live CTCs of any tumor type, not limited to CTCs of epithelial origin. Furthermore, we demonstrate for the first time that VACV was effective in preventing and reducing circulating tumor cells in mice bearing human tumor xenografts. Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer. Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Body Fluids*
  • DNA Primers
  • Heterografts
  • Humans
  • Male
  • Mice
  • Neoplasm Metastasis / therapy*
  • Oncolytic Virotherapy*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy
  • Vaccinia virus / physiology*

Substances

  • DNA Primers

Grant support

This work was supported by grants from Genelux Corporation (R&D facility in San Diego, CA). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.