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Canstatin gene electrotransfer combined with radiotherapy: preclinical trials for cancer treatment

Gene Therapy volume 15, pages 1436–1445 (2008)Cite this article

Abstract

Given as a prophylactic treatment, a single muscle electrogene transfer of plasmid coding canstatin fused to human serum albumin (CanHSA), slowed down the development of two xenografted human carcinomas from mammary (MDA-MB-231) and prostate origin (PC-3) in nude mice and delayed lung metastatic spreading of B16F10 melanoma cells in syngenic mice. No effect was observed with unfused canstatin. The long lasting circulating blood level of CanHSA (20 ng ml−1) resulted in a profound disorganization of the tumor blood vessel network. However, when used as a curative treatment, on well-established tumors, CanHSA electrogenetherapy was ineffective in reducing tumor growth. As radiation is known to increase the αvβ3 and αvβ5 integrins, which are canstatin receptors, to extend the use of CanHSA electrogenetherapy, as a curative treatment, we explored the combination of CanHSA and ionizing radiation. We demonstrated a better efficacy (P=0.01) of the bitherapy over irradiation alone, as a result of strong vessel disorganization and dramatic increase of tumor cells apoptosis. This extremely simple virus free curative protocol could open the door to potential clinical applications, especially for prostate cancer that often develops radioresistance.

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Acknowledgements

This paper was devoted to the memory of Patrice Ardouin, associate director of animal facility at Institut Gustave Roussy. We sincerely thank Monique Stanciu and Annie Rouches for excellent technical assistance and animal care. This work was supported by the Centre National de la Recherche Scientifique, the Institut Gustave Roussy, l'ARC Association de Recherche contre le Cancer, l'EDF (electricité de France) and University Paris XI. Claire Magnon was supported by Assistance Publique-Hôpitaux de Paris, the Institut National de la Santé et de la Recherche Médicale and Commissariat à l'Energie Atomique.

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Authors and Affiliations

  1. CNRS, UMR8121, Vectorologie et Transfert de Gènes, Villejuif, Cedex, France

    C Magnon, L M Mir, M Perricaudet & D Martel-Renoir

  2. CNRS, UMR8121, Université Paris-Sud, Villejuif, Cedex, France

    C Magnon, P Opolon, E Connault, L M Mir, M Perricaudet & D Martel-Renoir

  3. CNRS, UMR8121, Institut Gustave Roussy, Villejuif, Cedex, France

    C Magnon, P Opolon, E Connault, L M Mir, M Perricaudet & D Martel-Renoir

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Correspondence to D Martel-Renoir.

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Magnon, C., Opolon, P., Connault, E. et al. Canstatin gene electrotransfer combined with radiotherapy: preclinical trials for cancer treatment. Gene Ther 15, 1436–1445 (2008). https://doi.org/10.1038/gt.2008.100

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