806. Active Targeting of Bioreducible Polymer Concealing Oncolytic Adenovirus to Cancer Cells Expressing Integrins

The challenge of next-generation nanoparticles (NPs) includes limited cellular uptake and loss by phagocytosis. General surface modification of NPs potentially enhances evasion from phagocytosis. However, active targeting and enhanced cellular uptake of nanoparticles are possible by surface functionalisation with molecules that have selective affinity for cancer cells. ROR1 is a cell surface receptor that is over-expressed in cancer cells. Hence, its conjugate antibody could be a potential surface functionalisation molecule. In the current study, anti-ROR1 antibody has been covalently attached to nanoparticles’ surface, thereby imparting its active targeting potential. Physicochemical and in vitro characterisations of the antibody-conjugated nanoparticles were performed. Surface functionalisation of nanoparticles was confirmed by scanning electron microscopy, isothermal calorimetry, and elemental analysis. Additionally, biomarkers of metastasis and epithelial-mesenchymal transition (EMT) were studied. Anti-ROR1 mAb tagged nanoparticles further confirmed therapeutic efficacy against colon cancer cells, SW480, thus, opening scope for further in vivo studies.

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An Oncolytic Adenovirus Expressing SNORD44 and GAS5 Exhibits Antitumor Effect in Colorectal Cancer Cells

Human Gene Therapy ◽

10.1089/hum.2017.041 ◽

2017 ◽

Vol 28 (8) ◽

pp. 690-700 ◽

Cited By ~ 12

Author(s):

Sujing Yuan ◽

Yu Wu ◽

Yigang Wang ◽

Jianhua Chen ◽

Liang Chu

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Antitumor Effect ◽

Oncolytic Adenovirus ◽

Colorectal Cancer Cells

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579. CEACAM6 Attenuates the Potency of Oncolytic Adenovirus by Blocking Viral Trafficking Via the Src Pathway To Disturb the Cytoskeleton of Cancer Cells

Molecular Therapy ◽

10.1016/s1525-0016(16)39982-8 ◽

2008 ◽

Vol 16 ◽

pp. S217

Keyword(s):

Cancer Cells ◽

Oncolytic Adenovirus ◽

Src Pathway

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Effect of combined treatment of radiation and tissue-specific recombinant oncolytic adenovirus on bladder cancer cells

International Journal of Radiation Biology ◽

10.1080/09553002.2017.1231942 ◽

2016 ◽

Vol 93 (2) ◽

pp. 174-183 ◽

Cited By ~ 3

Author(s):

Hongjuan Zhang ◽

Fang Wang ◽

Chunjie Mao ◽

Zuncheng Zhang ◽

Shengjun Fu ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Combined Treatment ◽

Oncolytic Adenovirus ◽

Tissue Specific ◽

Bladder Cancer Cells

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Interferon-β-armed oncolytic adenovirus induces both apoptosis and necroptosis in cancer cells

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gms060 ◽

2012 ◽

Vol 44 (9) ◽

pp. 737-745 ◽

Cited By ~ 17

Author(s):

Hongling Huang ◽

Tian Xiao ◽

Lingfeng He ◽

Hongbin Ji ◽

Xin-Yuan Liu

Keyword(s):

Cancer Cells ◽

Oncolytic Adenovirus ◽

Interferon Β

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Novel Infectivity-Enhanced Oncolytic Adenovirus with a Capsid-Incorporated Dual-Imaging Moiety for Monitoring Virotherapy in Ovarian Cancer

Molecular Imaging ◽

10.2310/7290.2009.00025 ◽

2009 ◽

Vol 8 (5) ◽

pp. 7290.2009.00025 ◽

Cited By ~ 10

Author(s):

Kristopher J. Kimball ◽

Angel A. Rivera ◽

Kurt R. Zinn ◽

Mert Icyuz ◽

Vaibhav Saini ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Fluorescent Protein ◽

Imaging Modality ◽

Fluorescent Microscopy ◽

Oncolytic Adenovirus ◽

Ovarian Cancer Cells ◽

Microscopy Imaging ◽

Dual Imaging

We sought to develop a cancer-targeted, infectivity-enhanced oncolytic adenovirus that embodies a capsid-labeling fusion for non-invasive dual-modality imaging of ovarian cancer virotherapy. A functional fusion protein composed of fluorescent and nuclear imaging tags was genetically incorporated into the capsid of an infectivity-enhanced conditionally replicative adenovirus. Incorporation of herpes simplex virus thymidine kinase (HSV-tk) and monomeric red fluorescent protein 1 (mRFP1) into the viral capsid and its genomic stability were verified by molecular analyses. Replication and oncolysis were evaluated in ovarian cancer cells. Fusion functionality was confirmed by in vitro gamma camera and fluorescent microscopy imaging. Comparison of tk-mRFP virus to single-modality controls revealed similar replication efficiency and oncolytic potency. Molecular fusion did not abolish enzymatic activity of HSV-tk as the virus effectively phosphorylated thymidine both ex vivo and in vitro. In vitro fluorescence imaging demonstrated a strong correlation between the intensity of fluorescent signal and cytopathic effect in infected ovarian cancer cells, suggesting that fluorescence can be used to monitor viral replication. We have in vitro validated a new infectivity-enhanced oncolytic adenovirus with a dual-imaging modality-labeled capsid, optimized for ovarian cancer virotherapy. The new agent could provide incremental gains toward climbing the barriers for achieving conditionally replicated adenovirus efficacy in human trials.

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