title: 11R-P53 and GM-CSF Expressing Oncolytic Adenovirus Target Cancer Stem Cells with Enhanced Synergistic Activity.
abstract: Targeting cancer stem cells with oncolytic virus (OV) holds great potential for thorough elimination of cancer cells. Based on our previous studies, we here established 11R-P53 and mGM-CSF carrying oncolytic adenovirus (OAV) SG655-mGMP and investigated its therapeutic effect on hepatocellular carcinoma stem cells Hep3B-C and teratoma stem cells ECCG5. Firstly, the augmenting effect of 11R in our construct was tested and confirmed by examining the expression of EGFP with Fluorescence and FCM assays after transfecting Hep3B-C and ECCG5 cells with OVA SG7605-EGFP and SG7605-11R-EGFP. Secondly, the expressions of 11R-P53 and GM-CSF in Hep3B-C and ECCG5 cells after transfection with OAV SG655-mGMP were detected by Western blot and Elisa assays, respectively. Thirdly, the enhanced growth inhibitory and augmented apoptosis inducing effects of OAV SG655-mGMP on Hep3B-C and ECCG5 cells were tested with FCM assays by comparing with the control, wild type 5 adenovirus, 11R-P53 carrying OVAin vitro. Lastly, thein vivotherapeutic effect of OAV SG655-mGMP toward ECCG5 cell-formed xenografts was studied by measuring tumor volumes post different treatments with PBS, OAV SG655-11R-P53, OAV SG655-mGM-CSF and OAV SG655-mGMP. Treatment with OAV SG655-mGMP induced significant xenograft growth inhibition, inflammation factor AIF1 expression and immune cells infiltration. Therefore, our OAV SG655-mGMP provides a novel platform to arm OVs to target cancer stem cells.
authors.affiliation: Department of Viral and Gene Therapy Laboratory, Shanghai Eastern Heptobiliary Surgery Hospital, Shanghai, 200438, China.
authors.forename: Sai-Qun
authors.initials: SQ
authors.lastname: Lv
authors.affiliation: Department of Viral and Gene Therapy Laboratory, Shanghai Eastern Heptobiliary Surgery Hospital, Shanghai, 200438, China.
authors.forename: Zhen-Long
authors.initials: ZL
authors.lastname: Ye
authors.affiliation: Ningbo NO.5 Hospital (Ningbo Cancer Hospital), Ningbo 315201, China.
authors.forename: Pin-Yi
authors.initials: PY
authors.lastname: Liu
authors.affiliation: Department of Viral and Gene Therapy Laboratory, Shanghai Eastern Heptobiliary Surgery Hospital, Shanghai, 200438, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Viral and Gene Therapy Laboratory, Shanghai Eastern Heptobiliary Surgery Hospital, Shanghai, 200438, China.
authors.forename: Lin-Fang
authors.initials: LF
authors.lastname: Li
authors.affiliation: Department of Viral and Gene Therapy Laboratory, Shanghai Eastern Heptobiliary Surgery Hospital, Shanghai, 200438, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Viral and Gene Therapy Laboratory, Shanghai Eastern Heptobiliary Surgery Hospital, Shanghai, 200438, China.
authors.forename: Hai-Li
authors.initials: HL
authors.lastname: Zhu
authors.affiliation: Department of Viral and Gene Therapy Laboratory, Shanghai Eastern Heptobiliary Surgery Hospital, Shanghai, 200438, China.
authors.forename: Hua-Jun
authors.initials: HJ
authors.lastname: Jin
authors.affiliation: Department of Viral and Gene Therapy Laboratory, Shanghai Eastern Heptobiliary Surgery Hospital, Shanghai, 200438, China;; Ningbo NO.5 Hospital (Ningbo Cancer Hospital), Ningbo 315201, China.
authors.forename: Qi-Jun
authors.initials: QJ
authors.lastname: Qian
keywords: 11R.; GM-CSF; OAV; P53; cancer stem cells