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Polyethylenimine-mediated in vivo gene transfer of a transmembrane superantigen fusion construct inhibits B16 murine melanoma growth

Cancer Gene Therapy volume 15, pages 742–749 (2008)Cite this article

Abstract

Immunotherapy has been proposed as a therapeutic strategy in advanced-stage melanomas in which other therapeutic options have little effect. The Staphylococcus enterotoxin A (SEA) has been used to stimulate an antitumoral immune response but its use is hampered by severe systemic side effects. Here, we show that SEA can be targeted to melanoma cells to limit these side effects. More specifically, we used a nonviral vector, the cationic polymer, polyethylenimine (PEI), to express a transmembrane SEA fusion construct (pSEA-TM) in B16F10-induced subcutaneous melanoma in mice. The efficacy of this in vivo transfection was enhanced by concomitant infusion of epinephrine to induce local vasoconstriction. In these conditions, repeated injections of pSEA-TM/PEI complexes elicited a significant response, as evidenced by tumor growth inhibition, without systemic adverse effects. T cell infiltration of the tumors, together with positive lymphocyte proliferation tests, suggested local and systemic immune responses. Altogether, PEI-mediated targeting of SEA to melanoma tumor cells in vivo efficiently stimulates the antitumor immune response without inducing the side effects observed with systemic administration of SEA.

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Acknowledgements

The authors are grateful to Franck Ménétrier for his technical assistance and to Charles Thomas, Véronique Laurens and Pierre Emmanuel Puig for helpful discussions. This study was supported by grants from the ‘Ligue Nationale contre le Cancer’ (commitees of Alsace and Côte d’Or to JC; commitee of Nièvre for BC; national label to ES group).

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Authors and Affiliations

  1. Inserm U866, IFR100, Faculté de Médecine, Dijon, France

    G Jeudy, F Salvadori, B Chauffert, E Solary & J Chluba

  2. Dermatology Department, CHU Le Bocage, Dijon, France

    G Jeudy & P Vabres

  3. GF Leclerc Regional Anticancer Center, 1 rue du Professeur Marion, Dijon, France

    B Chauffert

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  1. G Jeudy
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Correspondence to J Chluba.

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Jeudy, G., Salvadori, F., Chauffert, B. et al. Polyethylenimine-mediated in vivo gene transfer of a transmembrane superantigen fusion construct inhibits B16 murine melanoma growth. Cancer Gene Ther 15, 742–749 (2008). https://doi.org/10.1038/cgt.2008.42

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