TY  - JOUR
A1  - Szalay, Aladar A
A1  - Weibel, Stephanie
A1  - Hofmann, Elisabeth
A1  - Basse-Luesebrink, Thomas Christian
A1  - Donat, Ulrike
A1  - Seubert, Carolin
A1  - Adelfinger, Marion
A1  - Gnamlin, Prisca
A1  - Kober, Christina
A1  - Frentzen, Alexa
A1  - Gentschev, Ivaylo
A1  - Jakob, Peter Michael
T1  - Treatment of malignant effusion by oncolytic virotherapy in an experimental subcutaneous xenograft model of lung cancer
JF  - Journal of Translational Medicine
N2  - Background

Malignant pleural effusion (MPE) is associated with advanced stages of lung cancer and is mainly dependent on invasion of the pleura and expression of vascular endothelial growth factor (VEGF) by cancer cells. As MPE indicates an incurable disease with limited palliative treatment options and poor outcome, there is an urgent need for new and efficient treatment options.

Methods

In this study, we used subcutaneously generated PC14PE6 lung adenocarcinoma xenografts in athymic mice that developed subcutaneous malignant effusions (ME) which mimic pleural effusions of the orthotopic model. Using this approach monitoring of therapeutic intervention was facilitated by direct observation of subcutaneous ME formation without the need of sacrificing mice or special imaging equipment as in case of MPE. Further, we tested oncolytic virotherapy using Vaccinia virus as a novel treatment modality against ME in this subcutaneous PC14PE6 xenograft model of advanced lung adenocarcinoma.

Results

We demonstrated significant therapeutic efficacy of Vaccinia virus treatment of both advanced lung adenocarcinoma and tumor-associated ME. We attribute the efficacy to the virus-mediated reduction of tumor cell-derived VEGF levels in tumors, decreased invasion of tumor cells into the peritumoral tissue, and to viral infection of the blood vessel-invading tumor cells. Moreover, we showed that the use of oncolytic Vaccinia virus encoding for a single-chain antibody (scAb) against VEGF (GLAF-1) significantly enhanced mono-therapy of oncolytic treatment.

Conclusions

Here, we demonstrate for the first time that oncolytic virotherapy using tumor-specific Vaccinia virus represents a novel and promising treatment modality for therapy of ME associated with advanced lung cancer.
KW  - Oncolytic virotherapy
KW  - Malignant effusion
KW  - Lung cancer
KW  - VEGF
KW  - Lungenkrebs
KW  - Vascular endothelial Growth Factor
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96016
UR  - http://www.translational-medicine.com/content/11/1/106
ER  - 
TY  - JOUR
A1  - Gentschev, Ivaylo
A1  - Adelfinger, Marion
A1  - Josupeit, Rafael
A1  - Rudolph, Stephan
A1  - Ehrig, Klaas
A1  - Donat, Ulrike
A1  - Weibel, Stephanie
A1  - Chen, Nanhai G.
A1  - Yu, Yong A.
A1  - Zhang, Qian
A1  - Heisig, Martin
A1  - Thamm, Douglas
A1  - Stritzker, Jochen
A1  - MacNeill, Amy
A1  - Szalay, Aladar A.
T1  - Preclinical Evaluation of Oncolytic Vaccinia Virus for Therapy of Canine Soft Tissue Sarcoma
JF  - PLoS One
N2  - Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for canine cancer therapy. In this study we describe the establishment of an in vivo model of canine soft tissue sarcoma (CSTS) using the new isolated cell line STSA-1 and the analysis of the virus-mediated oncolytic and immunological effects of two different Lister VACV LIVP1.1.1 and GLV-1h68 strains against CSTS. Cell culture data demonstrated that both tested VACV strains efficiently infected and destroyed cells of the canine soft tissue sarcoma line STSA-1. In addition, in our new canine sarcoma tumor xenograft mouse model, systemic administration of LIVP1.1.1 or GLV-1h68 viruses led to significant inhibition of tumor growth compared to control mice. Furthermore, LIVP1.1.1 mediated therapy resulted in almost complete tumor regression and resulted in long-term survival of sarcoma-bearing mice. The replication of the tested VACV strains in tumor tissues led to strong oncolytic effects accompanied by an intense intratumoral infiltration of host immune cells, mainly neutrophils. These findings suggest that the direct viral oncolysis of tumor cells and the virus-dependent activation of tumor-associated host immune cells could be crucial parts of anti-tumor mechanism in STSA-1 xenografts. In summary, the data showed that both tested vaccinia virus strains and especially LIVP1.1.1 have great potential for effective treatment of CSTS.
KW  - breast-tumors
KW  - animal-model
KW  - nude-mice
KW  - cell-line
KW  - in-vitro
KW  - glv-1h68
KW  - cancer
KW  - virotherapy
KW  - dogs
KW  - neutrophils
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129998
VL  - 7
IS  - 5
ER  -