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Intravascular injections of a conditional replicative adenovirus (adl118) prevent metastatic disease in human breast carcinoma xenografts

Gene Therapy volume 8, pages 1627–1634 (2001)Cite this article

Abstract

We describe a study showing that the adenovirus adl118, lacking both E1B proteins, very efficiently kills human malignant cells ‘in vitro’ and ‘in vivo’. Since many breast cancer patients do not have metastasis at the time of diagnosis, but finally develop it, we planned to study whether intravascular injections of adl118 could prevent metastatic development. We studied the effects of this mutant adenovirus in an orthotopic model of human breast carcinoma xenografts with the breast MB435-lung 2 cell line, which is highly metastatic in the lungs. In this study, all primary tumors were excised when they reached 50–100 mm3 volume in the animals. After surgery, 1010 p.f.u. of adl118 was intravenously injected into a random group of animals, either three times during the first week only, or once every week. At death, almost all the control animals showed numerous lung metastases of large size, which were present in only 15–40% of the treated animals, depending on the size of the primary tumor at the time of excision. Overall survival was 50–70 days in control mice, and over 120 days in mice injected with adl118. Concomitant treatment with adl118 and cisplatin did not enhance the antitumor effects of adl118. With these results, we conclude that intravenous injection of conditional replicative adenovirus, after excision of the primary tumor, induces a clear decrease in the metastatic disease, and could be a new strategy in preventing tumor metastasis of breast carcinomas.

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Acknowledgements

We thank Dr R Alemany for providing the adGFP and for his critical reading of the manuscript. We thank S Jones for preparing the manuscript, Isabel Millan for the statistical anaylsis and Javier Hernandez for the in vivo studies. This work was supported by grants from the ‘Fondo Español de Investigaciones Sanitarias’, FIS 99/0504, and FIS 00/ 903 (AF); the Comunidad de Madrid, CAM 98/08.1/2, Aventis; and the Areces Foundation.

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Authors and Affiliations

  1. Department of Pathology, Clínica Puerta de Hierro, Madrid, Spain

    C Parada, P Martín Duque, V Fernandez, R Sanchez-Prieto & S Ramon y Cajal

  2. Institute of Recerca Oncologica, Barcelona, Spain

    A Fabra & A Vinyals

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  1. A Fabra
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  2. C Parada
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  3. A Vinyals
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  4. P Martín Duque
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Fabra, A., Parada, C., Vinyals, A. et al. Intravascular injections of a conditional replicative adenovirus (adl118) prevent metastatic disease in human breast carcinoma xenografts. Gene Ther 8, 1627–1634 (2001). https://doi.org/10.1038/sj.gt.3301567

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