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Effect of fractalkine-Fc delivery in experimental lung metastasis using DNA/704 nanospheres

Cancer Gene Therapy volume 18, pages 761–772 (2011)Cite this article

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Abstract

The lung is one target organ to which solid tumors frequently metastasize. Given the systemic adverse effects of currently available treatments, developing effective strategies of drug/gene delivery directly to the lungs is therefore needed. Aerosol delivery is a non-invasive gene transfer approach to target the airways. Here, we sought to evaluate the potential to deliver a fractalkine (FKN)-encoding plasmid formulated with the tetrafunctional amphiphilic block copolymer 704 through aerosolization in two models of pulmonary metastases. FKN is a chemokine recently described as a good candidate to stimulate a strong antitumor immune response in various forms of cancers. Here, we have assessed the effect of single and repeated aerosolizations of FKN-encoding plasmid formulated with 704 on the development of experimental lung metastases of mouse colon carcinoma and osteosarcoma. For this purpose, we have designed FKN-Fc sequences encoding an optimized version of the chemokine. Repeated intratracheal administrations of 704/FKN-Fc markedly inhibited growth of experimental lung metastases of CT-26 and K7M2 cells. Our results showed that tetrafunctional amphiphilic block copolymer 704 is a highly efficient synthetic vector for mediating local and safe gene transfer into the lung. In addition, FKN-Fc gene therapy of pulmonary nodules may provide a promising immunotherapeutic approach.

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Abbreviations

FKN:

fractalkine

PEI:

polyethyleneimine

CAT:

chloramphenicol acetyl transferase

IL-6:

interleukin-6

NK cell:

natural killer cell

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Acknowledgements

We thank Violette Breittmayer for excellent technical assistance, Clothilde Gourden for excellent technical expertise in in vivo experiments, In-Cell-Art for providing tetrafunctional amphiphilic block copolymers and the Animal Facility of the Centre Méditerranéen de Médecine Moléculaire (Institut National de la Santé et de la Recherche Médicale, Unit 895). This research was supported in part by the Institut National de la Santé et de la Recherche Médicale, by the Centre National de la Recherche Scientifique, by the Association pour la Recherche sur le Cancer (ARC, Grant 3707), by Vaincre La Mucoviscidose (Paris, France) and the Association Française contre les Myopathies (Evry, France). PR-F was the recipient of a fellowship from the ARC.

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Author notes

  1. H Schmid-Antomarchi and A Schmid-Alliana: These authors contributed equally to this work.

Authors and Affiliations

  1. INSERM, UMR576, CHU Archet I, Nice, France

    P Richard-Fiardo, B Cambien, E Pradelli, H Schmid-Antomarchi & A Schmid-Alliana

  2. Université Nice Sophia Antipolis, UFR Médecine, Nice, France

    P Richard-Fiardo, B Cambien, E Pradelli, H Schmid-Antomarchi & A Schmid-Alliana

  3. INSERM UMR915, Institut du thorax, Nantes, France

    F Beilvert & B Pitard

  4. Université de Nantes, UFR Médecine, Nantes, France

    F Beilvert & B Pitard

  5. In-Cell-Art, Nantes, France

    B Pitard

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  1. P Richard-Fiardo
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Corresponding author

Correspondence to A Schmid-Alliana.

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Competing interests

The authors declare no conflict of interest, except B Pitard who owns stocks in In-Cell-Art Co., which commercializes amphiphilic block copolymers.

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Richard-Fiardo, P., Cambien, B., Pradelli, E. et al. Effect of fractalkine-Fc delivery in experimental lung metastasis using DNA/704 nanospheres. Cancer Gene Ther 18, 761–772 (2011). https://doi.org/10.1038/cgt.2011.42

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  • DOI: https://doi.org/10.1038/cgt.2011.42

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