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Molecular Cancer Therapeutics
Molecular Cancer Therapeutics
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Small Molecule Therapeutics

Oncolytic Adenovirus Loaded with L-carnosine as Novel Strategy to Enhance the Antitumor Activity

Mariangela Garofalo, Barbara Iovine, Lukasz Kuryk, Cristian Capasso, Mari Hirvinen, Andrea Vitale, Marjo Yliperttula, Maria Assunta Bevilacqua and Vincenzo Cerullo
Mariangela Garofalo
1Laboratory of ImmunoViroTherapy, Centre for Drug Research (CDR), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
2Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples, Italy.
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Barbara Iovine
2Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples, Italy.
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Lukasz Kuryk
1Laboratory of ImmunoViroTherapy, Centre for Drug Research (CDR), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
3Oncos Therapeutics Ltd., Helsinki, Finland.
4Department of Virology, National Institute of Public Health–National Institute of Hygiene, Warsaw, Poland.
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Cristian Capasso
1Laboratory of ImmunoViroTherapy, Centre for Drug Research (CDR), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
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Mari Hirvinen
1Laboratory of ImmunoViroTherapy, Centre for Drug Research (CDR), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
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Andrea Vitale
5Department of Movement Sciences and Wellness (DiSMEB), University of Naples Parthenope and CEINGE-Biotecnologie Avanzate, Naples, Italy.
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Marjo Yliperttula
6Division of Pharmaceutical Biosciences and Centre for Drug Research, University of Helsinki, Helsinki, Finland.
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Maria Assunta Bevilacqua
2Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples, Italy.
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Vincenzo Cerullo
1Laboratory of ImmunoViroTherapy, Centre for Drug Research (CDR), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
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  • For correspondence: vincenzo.cerullo@helsinki.fi
DOI: 10.1158/1535-7163.MCT-15-0559 Published April 2016
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Abstract

Oncolytic viruses are able to specifically replicate, infect, and kill only cancer cells. Their combination with chemotherapeutic drugs has shown promising results due to the synergistic action of virus and drugs; the combinatorial therapy is considered a potential clinically relevant approach for cancer. In this study, we optimized a strategy to absorb peptides on the viral capsid, based on electrostatic interaction, and used this strategy to deliver an active antitumor drug. We used L-carnosine, a naturally occurring histidine dipeptide with a significant antiproliferative activity. An ad hoc modified, positively charged L-carnosine was combined with the capsid of an oncolytic adenovirus to generate an electrostatic virus–carnosine complex. This complex showed enhanced antitumor efficacy in vitro and in vivo in different tumor models. In HCT-116 colorectal and A549 lung cancer cell lines, the complex showed higher transduction ratio and infectious titer compared with an uncoated oncolytic adenovirus. The in vivo efficacy of the complex was tested in lung and colon cancer xenograft models, showing a significant reduction in tumor growth. Importantly, we investigated the molecular mechanisms underlying the effects of complex on tumor growth reduction. We found that complex induces apoptosis in both cell lines, by using two different mechanisms, enhancing viral replication and affecting the expression of Hsp27. Our system could be used in future studies also for delivery of other bioactive drugs. Mol Cancer Ther; 15(4); 651–60. ©2016 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

  • Received July 15, 2015.
  • Revision received January 15, 2016.
  • Accepted January 30, 2016.
  • ©2016 American Association for Cancer Research.
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Molecular Cancer Therapeutics: 15 (4)
April 2016
Volume 15, Issue 4
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Oncolytic Adenovirus Loaded with L-carnosine as Novel Strategy to Enhance the Antitumor Activity
Mariangela Garofalo, Barbara Iovine, Lukasz Kuryk, Cristian Capasso, Mari Hirvinen, Andrea Vitale, Marjo Yliperttula, Maria Assunta Bevilacqua and Vincenzo Cerullo
Mol Cancer Ther April 1 2016 (15) (4) 651-660; DOI: 10.1158/1535-7163.MCT-15-0559

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Oncolytic Adenovirus Loaded with L-carnosine as Novel Strategy to Enhance the Antitumor Activity
Mariangela Garofalo, Barbara Iovine, Lukasz Kuryk, Cristian Capasso, Mari Hirvinen, Andrea Vitale, Marjo Yliperttula, Maria Assunta Bevilacqua and Vincenzo Cerullo
Mol Cancer Ther April 1 2016 (15) (4) 651-660; DOI: 10.1158/1535-7163.MCT-15-0559
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Molecular Cancer Therapeutics
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