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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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Detection and identification of live tumor cells in a CSF sample.(A) The live tumor cells in the CSF sample of a patient with metastatic breast cancer were identified as TurboFP635+/CK+/DAPI+ cells. (B) A live cancer cell cluster with heterogeneous expression of CK in the CSF sample was identified by VACV.
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pone-0071105-g003: Detection and identification of live tumor cells in a CSF sample.(A) The live tumor cells in the CSF sample of a patient with metastatic breast cancer were identified as TurboFP635+/CK+/DAPI+ cells. (B) A live cancer cell cluster with heterogeneous expression of CK in the CSF sample was identified by VACV.

Mentions: CSF samples from seven patients with glioblastoma multiforme, metastatic colorectal carcinoma, metastatic breast cancer and metastatic esophageal cancer were analyzed using the VACV-cytospin assay (Table S5). The volume of each sample ranged from 3 to 5 mL. A total of 23 TurboFP635+ cells with large nuclei were found in the 3 mL CSF sample from the patient CSF7 with metastatic breast cancer (Figure 3). Among these, 16 cells showed high-level expression of CK (Figure 3A) and the rest of the infected cells showed very low level or no expression of CK (Figure 3B). No infected cells were found in the CSF samples from the other six patients. To confirm the absence of cancer cells in these six CSF samples, infected samples were further analyzed using immunostaining for CK. No CK+ cells were detected in these six patients that were negative for TurboFP635.


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)

Detection and identification of live tumor cells in a CSF sample.(A) The live tumor cells in the CSF sample of a patient with metastatic breast cancer were identified as TurboFP635+/CK+/DAPI+ cells. (B) A live cancer cell cluster with heterogeneous expression of CK in the CSF sample was identified by VACV.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0071105-g003: Detection and identification of live tumor cells in a CSF sample.(A) The live tumor cells in the CSF sample of a patient with metastatic breast cancer were identified as TurboFP635+/CK+/DAPI+ cells. (B) A live cancer cell cluster with heterogeneous expression of CK in the CSF sample was identified by VACV.
Mentions: CSF samples from seven patients with glioblastoma multiforme, metastatic colorectal carcinoma, metastatic breast cancer and metastatic esophageal cancer were analyzed using the VACV-cytospin assay (Table S5). The volume of each sample ranged from 3 to 5 mL. A total of 23 TurboFP635+ cells with large nuclei were found in the 3 mL CSF sample from the patient CSF7 with metastatic breast cancer (Figure 3). Among these, 16 cells showed high-level expression of CK (Figure 3A) and the rest of the infected cells showed very low level or no expression of CK (Figure 3B). No infected cells were found in the CSF samples from the other six patients. To confirm the absence of cancer cells in these six CSF samples, infected samples were further analyzed using immunostaining for CK. No CK+ cells were detected in these six patients that were negative for TurboFP635.

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