Abstract | BACKGROUND: 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:
|
Authors | Stephanie Weibel, Elisabeth Hofmann, Thomas Christian Basse-Luesebrink, Ulrike Donat, Carolin Seubert, Marion Adelfinger, Prisca Gnamlin, Christina Kober, Alexa Frentzen, Ivaylo Gentschev, Peter Michael Jakob, Aladar A Szalay |
Journal | Journal of translational medicine
(J Transl Med)
Vol. 11
Pg. 106
(May 01 2013)
ISSN: 1479-5876 [Electronic] England |
PMID | 23635329
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Single-Chain Antibodies
- Vascular Endothelial Growth Factor A
|
Topics |
- Animals
- Cell Line, Tumor
- Female
- Flow Cytometry
- Humans
- Injections, Subcutaneous
- Lung Neoplasms
(therapy)
- Magnetic Resonance Imaging
- Mice
- Mice, Nude
- Oncolytic Virotherapy
(methods)
- Oncolytic Viruses
(metabolism)
- Pleural Effusion, Malignant
(therapy)
- Single-Chain Antibodies
(chemistry)
- Treatment Outcome
- Vaccinia virus
(metabolism)
- Vascular Endothelial Growth Factor A
(metabolism)
- Xenograft Model Antitumor Assays
|