TY  - JOUR
A1  - Haddad, Dana
A1  - Chen, Nanhai G.
A1  - Zhang, Qian
A1  - Chen, Chun-Hao
A1  - Yu, Yong A.
A1  - Gonzalez, Lorena
A1  - Carpenter, Susanne G.
A1  - Carson, Joshua
A1  - Au, Joyce
A1  - Mittra, Arjun
A1  - Gonen, Mithat
A1  - Zanzonico, Pat B.
A1  - Fong, Yuman
A1  - Szalay, Aladar A.
T1  - Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus
JF  - Journal of Translational Medicine
N2  - Introduction: 

Oncolytic viruses show promise for treating cancer. However, to assess therapeutic efficacy and potential toxicity, a noninvasive imaging modality is needed. This study aimed to determine if insertion of the human sodium iodide symporter (hNIS) cDNA as a marker for non-invasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, GLV-1h153. 

Methods: 

GLV-1h153 was modified from parental vaccinia virus GLV-1h68 to carry hNIS via homologous recombination. GLV-1h153 was tested against human pancreatic cancer cell line PANC-1 for replication via viral plaque assays and flow cytometry. Expression and transportation of hNIS in infected cells was evaluated using Westernblot and immunofluorescence. Intracellular uptake of radioiodide was assessed using radiouptake assays. Viral cytotoxicity and tumor regression of treated PANC-1tumor xenografts in nude mice was also determined. Finally, tumor radiouptake in xenografts was assessed via positron emission tomography (PET) utilizing carrier-free (124)I radiotracer. 

Results: 

GLV-1h153 infected, replicated within, and killed PANC-1 cells as efficiently as GLV-1h68. GLV-1h153 provided dose-dependent levels of hNIS expression in infected cells. Immunofluorescence detected transport of the protein to the cell membrane prior to cell lysis, enhancing hNIS-specific radiouptake (P < 0.001). In vivo, GLV-1h153 was as safe and effective as GLV-1h68 in regressing pancreatic cancer xenografts (P < 0.001). Finally, intratumoral injection of GLV-1h153 facilitated imaging of virus replication in tumors via (124)I-PET. 

Conclusion: 

Insertion of the hNIS gene does not hinder replication or oncolytic capability of GLV-1h153, rendering this novel virus a promising new candidate for the noninvasive imaging and tracking of oncolytic viral therapy.
KW  - Human Sodium/Iodide symporter
KW  - Reporter gene
KW  - NA+/I-symporter
KW  - Nude-mice
KW  - Cancer
KW  - In-Vivo
KW  - Expression
KW  - Therapy
KW  - Transporter
KW  - GLV-1H68
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140847
VL  - 9
IS  - 36
ER  - 
TY  - JOUR
A1  - Gentschev, Ivaylo
A1  - Müller, Meike
A1  - Adelfinger, Marion
A1  - Weibel, Stephanie
A1  - Grummt, Friedrich
A1  - Zimmermann, Martina
A1  - Bitzer, Michael
A1  - Heisig, Martin
A1  - Zhang, Qian
A1  - Yu, Yong A.
A1  - Chen, Nanhai G.
A1  - Stritzker, Jochen
A1  - Lauer, Ulrich M.
A1  - Szalay, Aladar A.
T1  - Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68
JF  - PLOS ONE
N2  - Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In this study, we analyzed for the first time the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 in two human hepatocellular carcinoma cell lines HuH7 and PLC/PRF/5 (PLC) in cell culture and in tumor xenograft models. By viral proliferation assays and cell survival tests, we demonstrated that GLV-1h68 efficiently colonized, replicated in, and did lyse these cancer cells in culture. Experiments with HuH7 and PLC xenografts have revealed that a single intravenous injection (i.v.) of mice with GLV-1h68 resulted in a significant reduction of primary tumor sizes compared to uninjected controls. In addition, replication of GLV-1h68 in tumor cells led to strong inflammatory and oncolytic effects resulting in intense infiltration of MHC class II-positive cells like neutrophils, macrophages, B cells and dendritic cells and in up-regulation of 13 pro-inflammatory cytokines. Furthermore, GLV-1h68 infection of PLC tumors inhibited the formation of hemorrhagic structures which occur naturally in PLC tumors. Interestingly, we found a strongly reduced vascular density in infected PLC tumors only, but not in the non-hemorrhagic HuH7 tumor model. These data demonstrate that the GLV-1h68 vaccinia virus may have an enormous potential for treatment of human hepatocellular carcinoma in man.
KW  - Breast-tumors
KW  - Nude-mice
KW  - In-vivo
KW  - Cancer
KW  - Inhibitor
KW  - Tissue
KW  - Agent
KW  - COX-2
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135319
VL  - 6
IS  - 7
ER  -