A Novel Combination Treatment of Armed Oncolytic Adenovirus Expressing IL-12 and GM-CSF with Radiotherapy in Murine Hepatocarcinoma
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概要
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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 × 108 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.
- Journal of Radiation Research 編集委員会の論文
著者
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Koom Woong
Department Of Radiation Oncology Brain Korea 21 Project For Medical Science Yonsei University Health
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Kim Wonwoo
Department Of Radiation Oncology Brain Korea 21 Project For Medical Science Yonsei University Health
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Seong Jinsil
Department Of Radiation Oncology Brain Korea 21 Project For Medicine Yonsei University
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Seong Jinsil
Department Of Radiation Oncology : Brain Korea 21 Project For Medical Science : Institute For Gastro
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Oh Hae
Department Of Radiation Oncology Brain Korea 21 Project For Medicine Yonsei University
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CHOI Kyung-Joo
Institute for Cancer Research, Yonsei Cancer Center
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YUN Chae-Ok
Institute for Cancer Research, Yonsei Cancer Center
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- A Novel Combination Treatment of Armed Oncolytic Adenovirus Expressing IL-12 and GM-CSF with Radiotherapy in Murine Hepatocarcinoma
- A Novel Combination Treatment of Armed Oncolytic Adenovirus Expressing IL-12 and GM-CSF with Radiotherapy in Murine Hepatocarcinoma
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