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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

Therapy of cancer cells in the ascites of a cancer patient with peritoneal carcinomatosis.Cell block sections of malignant ascitic cells were stained with haematoxylin and eosin (A-I, B-I) at three (A) and seven (B) days after virus treatment. EpCAM positive cells in the malignant ascites sections were detected using an anti-EpCAM antibody (A-II, B-II). GL-ONC1 infection of single cells was detected using an anti-VACV-A27L antibody (A-III, B-III). Scale bars represent 50 µm.
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pone-0071105-g005: Therapy of cancer cells in the ascites of a cancer patient with peritoneal carcinomatosis.Cell block sections of malignant ascitic cells were stained with haematoxylin and eosin (A-I, B-I) at three (A) and seven (B) days after virus treatment. EpCAM positive cells in the malignant ascites sections were detected using an anti-EpCAM antibody (A-II, B-II). GL-ONC1 infection of single cells was detected using an anti-VACV-A27L antibody (A-III, B-III). Scale bars represent 50 µm.

Mentions: Tumor cell-containing ascites from a patient with PC from gastric cancer were isolated three and seven days after the first intraperitoneal treatment with 107 pfu of GL-ONC1 (clinical version of GLV-1h68). Ascitic cells were fixed in buffered formalin, and a cell block was made and paraffin embedded. Paraffin sections were stained with haematoxylin and eosin for morphologic evaluation. Using either anti-EpCAM or anti-vaccinia specific antibodies, around 5% of all cells were found to be EpCAM-positive three days after treatment, and only around 5–10% of these cancer cells were VACV positive at the same time point (Figure 5). The background population showed an evidence of significant acute inflammation with an increase in neutrophils. In contrast, four days later (i.e. 7 days after treatment), less than 2% of all ascitic cells were still EpCAM-positive, and more than 90% of these cancer cells were VACV positive. The VACV-positive cancer cells morphologically showed significant degenerative changes (in the process of cell death). These promising results suggest that GL-ONC1 can effectively remove live tumor cells in the ascites of patients with PC.


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)

Therapy of cancer cells in the ascites of a cancer patient with peritoneal carcinomatosis.Cell block sections of malignant ascitic cells were stained with haematoxylin and eosin (A-I, B-I) at three (A) and seven (B) days after virus treatment. EpCAM positive cells in the malignant ascites sections were detected using an anti-EpCAM antibody (A-II, B-II). GL-ONC1 infection of single cells was detected using an anti-VACV-A27L antibody (A-III, B-III). Scale bars represent 50 µm.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0071105-g005: Therapy of cancer cells in the ascites of a cancer patient with peritoneal carcinomatosis.Cell block sections of malignant ascitic cells were stained with haematoxylin and eosin (A-I, B-I) at three (A) and seven (B) days after virus treatment. EpCAM positive cells in the malignant ascites sections were detected using an anti-EpCAM antibody (A-II, B-II). GL-ONC1 infection of single cells was detected using an anti-VACV-A27L antibody (A-III, B-III). Scale bars represent 50 µm.
Mentions: Tumor cell-containing ascites from a patient with PC from gastric cancer were isolated three and seven days after the first intraperitoneal treatment with 107 pfu of GL-ONC1 (clinical version of GLV-1h68). Ascitic cells were fixed in buffered formalin, and a cell block was made and paraffin embedded. Paraffin sections were stained with haematoxylin and eosin for morphologic evaluation. Using either anti-EpCAM or anti-vaccinia specific antibodies, around 5% of all cells were found to be EpCAM-positive three days after treatment, and only around 5–10% of these cancer cells were VACV positive at the same time point (Figure 5). The background population showed an evidence of significant acute inflammation with an increase in neutrophils. In contrast, four days later (i.e. 7 days after treatment), less than 2% of all ascitic cells were still EpCAM-positive, and more than 90% of these cancer cells were VACV positive. The VACV-positive cancer cells morphologically showed significant degenerative changes (in the process of cell death). These promising results suggest that GL-ONC1 can effectively remove live tumor cells in the ascites of patients with PC.

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