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

Wang H, Chen NG, Minev BR, Zimmermann M, Aguilar RJ, Zhang Q, Sturm JB, Fend F, Yu YA, Cappello J, Lauer UM, Szalay AA - PLoS ONE (2013)

Bottom Line: Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response.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.

View Article: PubMed Central - PubMed

Affiliation: Genelux Corporation, San Diego Science Center, San Diego, California, United States of America.

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.

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Related in: MedlinePlus

Prevention and therapy of CTCs in mice bearing human prostate cancer.(A) GLV-1h68 early treatment prevented CTC formation in the majority of mice (7/8) while mice in the PBS group showed an increase in CTC numbers. (B) GLV-1h68 late treatment resulted in a dramatic decrease in CTC numbers while CTC numbers in the PBS group increased greatly, and then fluctuated over time. (C) Almost all CTCs detected in the GLV-1h68 late treatment group were GFP-positive (infected) at two weeks after treatment. (D) Primary tumors regressed after GLV-1h68 early or late treatment. (E) Both GLV-1h68 early and late treatments significantly prolonged mouse survival (p = 0.002, GLV-1h68 early vs. PBS; p = 0.006 GLV-1h68 late vs. PBS).
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pone-0071105-g004: Prevention and therapy of CTCs in mice bearing human prostate cancer.(A) GLV-1h68 early treatment prevented CTC formation in the majority of mice (7/8) while mice in the PBS group showed an increase in CTC numbers. (B) GLV-1h68 late treatment resulted in a dramatic decrease in CTC numbers while CTC numbers in the PBS group increased greatly, and then fluctuated over time. (C) Almost all CTCs detected in the GLV-1h68 late treatment group were GFP-positive (infected) at two weeks after treatment. (D) Primary tumors regressed after GLV-1h68 early or late treatment. (E) Both GLV-1h68 early and late treatments significantly prolonged mouse survival (p = 0.002, GLV-1h68 early vs. PBS; p = 0.006 GLV-1h68 late vs. PBS).

Mentions: No CTCs were detected in any of the mice through 4 weeks after tumor cell implantation (prior to any treatment). All mice in the PBS-treated control group were CTC positive at one or more time points starting at 5 weeks after tumor cell implantation. In contrast, only one animal in the GLV-1h68 early treatment group had any detectable CTC’s after virus treatment (3, 1, and 2 CTCs at 2, 3, and 4 weeks after treatment, respectively, Figure 4A). Thus, early treatment significantly reduced CTC formation in mice bearing human prostate cancer tumors.


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

Wang H, Chen NG, Minev BR, Zimmermann M, Aguilar RJ, Zhang Q, Sturm JB, Fend F, Yu YA, Cappello J, Lauer UM, Szalay AA - PLoS ONE (2013)

Prevention and therapy of CTCs in mice bearing human prostate cancer.(A) GLV-1h68 early treatment prevented CTC formation in the majority of mice (7/8) while mice in the PBS group showed an increase in CTC numbers. (B) GLV-1h68 late treatment resulted in a dramatic decrease in CTC numbers while CTC numbers in the PBS group increased greatly, and then fluctuated over time. (C) Almost all CTCs detected in the GLV-1h68 late treatment group were GFP-positive (infected) at two weeks after treatment. (D) Primary tumors regressed after GLV-1h68 early or late treatment. (E) Both GLV-1h68 early and late treatments significantly prolonged mouse survival (p = 0.002, GLV-1h68 early vs. PBS; p = 0.006 GLV-1h68 late vs. PBS).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3760980&req=5

pone-0071105-g004: Prevention and therapy of CTCs in mice bearing human prostate cancer.(A) GLV-1h68 early treatment prevented CTC formation in the majority of mice (7/8) while mice in the PBS group showed an increase in CTC numbers. (B) GLV-1h68 late treatment resulted in a dramatic decrease in CTC numbers while CTC numbers in the PBS group increased greatly, and then fluctuated over time. (C) Almost all CTCs detected in the GLV-1h68 late treatment group were GFP-positive (infected) at two weeks after treatment. (D) Primary tumors regressed after GLV-1h68 early or late treatment. (E) Both GLV-1h68 early and late treatments significantly prolonged mouse survival (p = 0.002, GLV-1h68 early vs. PBS; p = 0.006 GLV-1h68 late vs. PBS).
Mentions: No CTCs were detected in any of the mice through 4 weeks after tumor cell implantation (prior to any treatment). All mice in the PBS-treated control group were CTC positive at one or more time points starting at 5 weeks after tumor cell implantation. In contrast, only one animal in the GLV-1h68 early treatment group had any detectable CTC’s after virus treatment (3, 1, and 2 CTCs at 2, 3, and 4 weeks after treatment, respectively, Figure 4A). Thus, early treatment significantly reduced CTC formation in mice bearing human prostate cancer tumors.

Bottom Line: Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response.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.

View Article: PubMed Central - PubMed

Affiliation: Genelux Corporation, San Diego Science Center, San Diego, California, United States of America.

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.

Show MeSH
Related in: MedlinePlus