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A novel combination treatment of armed oncolytic adenovirus expressing IL-12 and GM-CSF with radiotherapy in murine hepatocarcinoma

Authors
 Wonwoo KIM  ;  Jinsil SEONG  ;  Chae-Ok YUN  ;  Kyung-Joo CHOI  ;  Woong Sub KOOM  ;  Hae Jin OH 
Citation
 Journal of Radiation Research, Vol.52(5) : 646-654, 2011 
Journal Title
 Journal of Radiation Research 
ISSN
 0449-3060 
Issue Date
2011
Abstract
In this study, a novel combination treatment of armed oncolytic adenovirus expressing interleukin 12 (IL-12) and granulocyte-macrophage colony-stimulating factor (GM-CSF) with radiation was investigated for antitumor and antimetastatic effect in a murine hepatic cancer (HCa-I) model. Tumor bearing syngeneic mice were treated with radiation, armed oncolytic virus Ad-ΔE1Bmt7 (dB7) expressing both IL-12 and GM-CSF (armed dB7), or a combination of both. The adenovirus was administered by intratumoral injection 1 × 10(8) PFU per tumor in 50 µl of PBS four times every other day. Tumor response to treatment was determined by a tumor growth delay assay. Metastatic potential was evaluated by a lung metastasis model. To understand the underlying mechanism, the level of apoptosis was examined as well as the change in microvessel density and expression of immunological markers: CD4+, CD8+ and Cd11c. The combination of armed dB7 and radiation resulted in significant growth delay of murine hepatic cancer, HCa-1, with an enhancement factor of 4.3. The combination treatment also resulted in significant suppression of lung metastasis. Increase of apoptosis level as well as decrease of microvessel density was shown in the combination treatment, suggesting an underlying mechanism for the enhancement of antitumor effect. Expression of immunological markers: CD4+, CD8+ and Cd11c also increased in the combination treatment. This study showed that a novel combination treatment of radiotherapy with armed oncolytic adenovirus expressing IL-12 and GM-CSF was effective in suppressing primary tumor growth.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/94357
DOI
10.1269/jrr.10185
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터)
Yonsei Authors
금웅섭(Koom, Woong Sub) ; 김원우(Kim, Won Woo) ; 성진실(Seong, Jin Sil) ; 오해진(Oh, Hae Jin) ; 최경주(Choi, Kyung Ju)
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