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Journal of Translational Medicine

, 11:106

Immunobiology and immunotherapy

Abstract

BackgroundMalignant 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.

MethodsIn 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.

ResultsWe 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.

ConclusionsHere, 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.

KeywordsOncolytic virotherapy Malignant effusion Lung cancer VEGF AbbreviationsdpiDays post infection

dpimDays post implantation

ELISAEnzyme-linked immunosorbent assay

FACSFluorescence-activated cell sorting

FBSFetal bovine serum

Gd-DTPAGadopentetate-Dimeglumine

GFPGreen fluorescent protein

ivIntravenous

MEMalignant effusion

MPEMalignant pleural effusion

MRIMagnetic resonance imaging

MSEMulti spin echo

pfuPlaque forming unit

PIPropidium iodide

RFPRed fluorescent protein

rVACVRecombinant Vaccinia virus strain

scSubcutaneous

scAbSingle-chain antibody

SNRSignal to noise ratio

T1wT1 weighted

T2wT2 weighted

TCCBVTumor cell-containg blood vessel

VEGFVascular endothelial growth factor.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-11-106 contains supplementary material, which is available to authorized users.

Stephanie Weibel, Elisabeth Hofmann contributed equally to this work.

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Autor: Stephanie Weibel - Elisabeth Hofmann - Thomas Christian Basse-Luesebrink - Ulrike Donat - Carolin Seubert - Marion Adelfing

Fuente: https://link.springer.com/







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