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Eradication of glioblastoma by immuno-virotherapy with a retargeted oncolytic HSV in a preclinical model

Oncogene volume 38, pages 4467–4479 (2019)Cite this article

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Abstract

Oncolytic herpes simplex viruses are proving to be effective in clinical trials against a number of cancers. Here, R-115, an oncolytic herpes simplex virus retargeted to human erbB-2, fully virulent in its target cells, and armed with murine interleukin-12 was evaluated in a murine model of glioblastoma. We show that a single R-115 injection in established tumors resulted, in about 30% of animals, in the complete eradication of the tumor, otherwise invariably lethal. The treatment also induced a significant improvement in the overall median survival time of mice and a resistance to recurrence from the same neoplasia. Such a high degree of protection was unprecedented; it was not observed before following treatments with the commonly used, mutated/attenuated oncolytic viruses. This is the first study providing the evidence of benefits offered by a fully virulent, retargeted, and armed herpes simplex virus in the treatment of glioblastoma and paves the way for clinical translation.

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Acknowledgments

This work was supported by European Research Council (ERC) advanced grant number 340060 to GCF and PM; by Compagnia di San Paolo, Turin, Italy (grant no 2015.9834) “Terapie innovative per il glioblastoma” to PM; by RFO (University of Bologna) to LM and EA. We would like to thank Dr. Antonio Daga for providing human glioma-initiating cells.

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Authors and Affiliations

  1. Department of Experimental Medicine, University of Genoa, Genoa, Italy

    Francesco Alessandrini, Irene Appolloni, Davide Ceresa, Daniela Marubbi & Paolo Malatesta

  2. Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy

    Laura Menotti & Elisa Avitabile

  3. Ospedale Policlinico San Martino - IRCCS per l’Oncologia, Genoa, Italy

    Daniela Marubbi & Paolo Malatesta

  4. Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy

    Gabriella Campadelli-Fiume

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  1. Francesco Alessandrini
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  2. Laura Menotti
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  3. Elisa Avitabile
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  4. Irene Appolloni
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Correspondence to Paolo Malatesta.

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GCF owns shares in Nouscom. GCF and LM receive equity payments from Amgen. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; and in the writing of the manuscript. The other authors declare that they have no conflict of interest.

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Alessandrini, F., Menotti, L., Avitabile, E. et al. Eradication of glioblastoma by immuno-virotherapy with a retargeted oncolytic HSV in a preclinical model. Oncogene 38, 4467–4479 (2019). https://doi.org/10.1038/s41388-019-0737-2

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