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11R-P53 and GM-CSF Expressing Oncolytic Adenovirus Target Cancer Stem Cells with Enhanced Synergistic Activity

Sai-Qun Lv1, Zhen-Long Ye1, Pin-Yi Liu2

  • 1Department of Viral and Gene Therapy Laboratory, Shanghai Eastern Heptobiliary Surgery Hospital, Shanghai, 200438, China.

Journal of Cancer
|March 1, 2017
PubMed

Insights

This study developed a novel oncolytic adenovirus (OAV) SG655-mGMP, engineered to target cancer stem cells. The OAV demonstrated significant therapeutic effects, inhibiting tumor growth and promoting apoptosis in hepatocellular carcinoma and teratoma stem cells both in vitro and in vivo.

Area of Science:

  • Oncolytic virotherapy
  • Cancer stem cell biology
  • Gene therapy

Background:

  • Cancer stem cells (CSCs) are crucial for tumor recurrence and metastasis.
  • Oncolytic viruses (OVs) show promise in targeting and eliminating cancer cells.
  • Engineering OVs to target CSCs is a promising therapeutic strategy.

Purpose of the Study:

  • To establish and evaluate a novel oncolytic adenovirus (OAV) SG655-mGMP, armed with 11R-P53 and mGM-CSF.
  • To investigate the therapeutic efficacy of OAV SG655-mGMP against hepatocellular carcinoma stem cells (Hep3B-C) and teratoma stem cells (ECCG5).

Main Methods:

  • Constructed OAV SG655-mGMP carrying 11R-P53 and mGM-CSF.
  • Assessed 11R augmentation using EGFP expression (Fluorescence, FCM).
  • Detected 11R-P53 and GM-CSF expression (Western blot, ELISA).
  • Evaluated in vitro growth inhibition and apoptosis induction (FCM).
  • Studied in vivo therapeutic effects on xenografts (tumor volume measurement).

Main Results:

  • OAV SG655-mGMP demonstrated enhanced growth inhibition and apoptosis induction in CSCs in vitro.
  • In vivo treatment with OAV SG655-mGMP significantly inhibited xenograft growth.
  • OAV SG655-mGMP treatment increased inflammation factor AIF1 expression and immune cell infiltration in tumors.

Conclusions:

  • OAV SG655-mGMP effectively targets and eliminates cancer stem cells.
  • The engineered OAV exhibits potent anti-tumor activity both in vitro and in vivo.
  • OAV SG655-mGMP represents a novel platform for arming OVs to target CSCs.
Keywords:
11R.GM-CSFOAVP53cancer stem cells

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