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Local delivery of recombinant vaccinia virus encoding for neu counteracts growth of mammary tumors more efficiently than systemic delivery in neu transgenic mice

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Abstract

Recombinant vaccinia virus has been widely employed as a cancer vaccine in several clinical trials. In this study we explored, employing BALB/c mice transgenic for the rat neu oncogene, the ability of the recombinant vaccinia virus neu (rV-neuT) vaccine to inhibit growth of neu+ mammary carcinomas and whether the efficacy of vaccination was dependent on: (a) carcinogenesis stage at which the vaccination was initiated; (b) number of vaccinations and (c) route of delivery (systemic vs. local). BALB-neuT mice were vaccinated one, two and three times by subcutaneous (s.c.) and intramammary gland (im.g.) injection with rV-neuT or V-wt (wild-type vaccinia virus) starting at the stage in which mouse mammary gland displays atypical hyperplasia, carcinoma in situ or invasive carcinoma. We demonstrated that vaccination using rV-neuT was more effective when started at an earlier stage of mammary carcinogenesis and after three vaccinations. The im.g. vaccination was more effective than the s.c. vaccination in inhibiting mammary carcinogenesis, eliciting anti-Neu antibodies, increasing anti-Neu IgG2a/G3 isotypes and inducing antibodies able to trigger mammary tumor cells apoptosis and antibody-dependent cellular cytotoxicity. The better protective ability of rV-neuT im.g. vaccination was associated with its capacity to induce a superior degree of in vivo mammary cancer cells apoptosis. Our research suggests that intratumoral vaccination using recombinant vaccinia virus could be employed to increase the activity of a genetic cancer vaccine. This study may have important implications for the design of cancer vaccine protocols for the treatment of breast cancer and of accessible tumors using recombinant vaccinia virus.

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Acknowledgments

This study was supported by grants from PRIN and AIRC. We wish to thank Therion Biologics (Cambridge, MA) and Dr. G. Mazzara, which kindly provided vaccinia viruses, IRBM P. Angeletti (Pomezia, Rome) for peptides, and Dr. Eddi Di Marco (Istituto Tumori di Genova) for providing LTR-Neu cells. The authors thank Debra Weingarten for her editorial assistance in the preparation of the manuscript.

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Authors and Affiliations

  1. Department of Experimental Medicine, University of Rome ‘Sapienza’, Rome, Italy

    Laura Masuelli & Antonio Scardino

  2. Department of Experimental Medicine and Biochemical Sciences, University of Rome “Tor Vergata”, Via Montpellier 1, 00133, Rome, Italy

    Laura Marzocchella, Andrea Modesti & Roberto Bei

  3. Department of Biology, STA, University of Rome “Tor Vergata”, Rome, Italy

    Chiara Focaccetti & Maurizio Mattei

  4. Centro Studi e Ricerche Sanità e Veterinaria Esercito, Rome, Italy

    Florigio Lista

  5. Department of Mathematics, University of Rome “Tor Vergata”, Rome, Italy

    Alessandra Nardi

  6. Department of Internal Medicine, University ‘Tor Vergata’, Rome, Italy

    Mario Turriziani

  7. Department of Surgery, University of Rome ‘Sapienza’, Rome, Italy

    Mauro Modesti

  8. Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy

    Guido Forni

  9. Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Jeffrey Schlom

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  1. Laura Masuelli
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Correspondence to Roberto Bei.

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Masuelli, L., Marzocchella, L., Focaccetti, C. et al. Local delivery of recombinant vaccinia virus encoding for neu counteracts growth of mammary tumors more efficiently than systemic delivery in neu transgenic mice. Cancer Immunol Immunother 59, 1247–1258 (2010). https://doi.org/10.1007/s00262-010-0850-0

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