title: Optical detection and virotherapy of live metastatic tumor cells in body fluids with vaccinia strains.
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.
authors.affiliation: Genelux Corporation, San Diego Science Center, San Diego, California, United States of America.
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Wang
authors.forename: Nanhai G
authors.initials: NG
authors.lastname: Chen
authors.forename: Boris R
authors.initials: BR
authors.lastname: Minev
authors.forename: Martina
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Aguilar
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Julia B
authors.initials: JB
authors.lastname: Sturm
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Yong A
authors.initials: YA
authors.lastname: Yu
authors.forename: Joseph
authors.initials: J
authors.lastname: Cappello
authors.forename: Ulrich M
authors.initials: UM
authors.lastname: Lauer
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
mesh_terms: D000818:Animals; D001483:Base Sequence; D001826:Body Fluids; D017931:DNA Primers; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis / Q000628:therapy*; D050130:Oncolytic Virotherapy; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy; D014616:Vaccinia virus / Q000502:physiology*
chemical_list: D017931:DNA Primers
references.citation: Biomed Microdevices. 2009 Aug;11(4):883-92
references.pmid: 19387837
references.citation: PLoS One. 2012;7(9):e45942
references.pmid: 23049897
references.citation: Pathobiology. 2012;79(4):195-208
references.pmid: 22488297
references.citation: J Neurooncol. 2012 Jan;106(2):225-34
references.pmid: 21874597
references.citation: Int J Oncol. 2005 Jul;27(1):49-57
references.pmid: 15942643
references.citation: J Biomed Biotechnol. 2010;2010:489759
references.pmid: 20379368
references.citation: Surgery. 2009 Sep;146(3):498-505
references.pmid: 19715807
references.citation: Cancer Res. 2007 Oct 15;67(20):10038-46
references.pmid: 17942938
references.citation: J Oncol. 2010;2010:617421
references.pmid: 20016752
references.citation: Cancer Invest. 2012 Mar;30(3):209-24
references.pmid: 22360361
references.citation: Clin Cancer Res. 2004 Oct 15;10(20):6897-904
references.pmid: 15501967
references.citation: J Clin Invest. 2009 Oct;119(10):3172-81
references.pmid: 19729837
references.citation: J Transl Med. 2011 Sep 27;9:164
references.pmid: 21951588
references.citation: PLoS One. 2012;7(5):e37239
references.pmid: 22615950
references.citation: Semin Cancer Biol. 2012 Jun;22(3):234-49
references.pmid: 22484561
references.citation: Expert Rev Mol Diagn. 2012 Apr;12(3):303-12
references.pmid: 22468820
references.citation: Viruses. 2012 May;4(5):688-707
references.pmid: 22754644
references.citation: Hum Pathol. 2004 Jan;35(1):122-8
references.pmid: 14745734
references.citation: Nat Methods. 2007 Sep;4(9):741-6
references.pmid: 17721542
references.citation: Virol J. 2004 Nov 22;1:10
references.pmid: 15555076
references.citation: Clin Cancer Res. 2003 Jul;9(7):2598-604
references.pmid: 12855636
references.citation: J Mammary Gland Biol Neoplasia. 2010 Jun;15(2):261-73
references.pmid: 20449641
references.citation: Mol Med. 2011;17(7-8):628-34
references.pmid: 21487639
references.citation: Clin Cancer Res. 2008 Nov 1;14(21):7004-10
references.pmid: 18980996
references.citation: Curr Opin Oncol. 2010 Nov;22(6):627-35
references.pmid: 20689429
references.citation: Breast Cancer Res Treat. 2011 Aug;128(3):765-73
references.pmid: 21630023
references.citation: Cancer Gene Ther. 2013 Jan;20(1):25-32
references.pmid: 23196273
references.citation: Hepatogastroenterology. 2010 Sep-Oct;57(102-103):1173-7
references.pmid: 21410053
references.citation: Cancer Res. 2010 Jul 15;70(14):5649-69
references.pmid: 20610625
references.citation: Mol Cancer Ther. 2008 Sep;7(9):2894-903
references.pmid: 18790770
references.citation: Science. 2011 Mar 25;331(6024):1559-64
references.pmid: 21436443
references.citation: Cancer Res. 2011 Sep 15;71(18):5955-60
references.pmid: 21896640