title: Effect of fractalkine-Fc delivery in experimental lung metastasis using DNA/704 nanospheres.
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.
authors.affiliation: Archet I, Nice, France.
authors.forename: P
authors.initials: P
authors.lastname: Richard-Fiardo
authors.forename: B
authors.initials: B
authors.lastname: Cambien
authors.forename: E
authors.initials: E
authors.lastname: Pradelli
authors.forename: F
authors.initials: F
authors.lastname: Beilvert
authors.forename: B
authors.initials: B
authors.lastname: Pitard
authors.forename: H
authors.initials: H
authors.lastname: Schmid-Antomarchi
authors.forename: A
authors.initials: A
authors.lastname: Schmid-Alliana
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D045744:Cell Line, Tumor; D054428:Chemokine CX3CL1 / Q000235:genetics*; D016503:Drug Delivery Systems; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics*; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D054118:Nanospheres; D009362:Neoplasm Metastasis; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection
chemical_list: D054428:Chemokine CX3CL1; D007128:Immunoglobulin Fragments