title: Recombinant AAV-mediated in vivo long-term expression and antitumour activity of an anti-ganglioside GM3(Neu5Gc) antibody.
abstract: The ganglioside GM3(Neu5Gc) has gained increasing attention as therapeutic target because of its selective expression in various human tumours, such as melanoma, breast and lung cancer. 14F7 is a mouse IgG1 with specific reactivity to GM3(Neu5Gc)-positive tumours. The therapeutic activity of 14F7 has also been demonstrated in vivo, through its repetitive passive administration in tumour-bearing animals. In this work we used an alternative strategy to deliver recombinant 14F7 in vivo and analysed the therapeutic efficacy of this approach. We engineered a recombinant adeno-associated vector to direct the expression of secretable recombinant 14F7 in BALB/c animals. A single administration of the rAAV induced efficient production and secretion of the antibody in the bloodstream, with an expression level reaching plateau at ∼3 weeks after injection and persisting for almost a year. Strikingly, upon challenge with GM3(Neu5Gc)-positive X63-AG8.653 myeloma cells, tumour development was significantly delayed in animals treated with rAAV-14F7 with respect to animals treated with a control rAAV codifying for an irrelevant antibody. Finally, no significant differences in survival proportion were detected in animals injected with rAAV-14F7 or treated by standard administration of repetitive doses of purified monoclonal antibody 14F7.
authors.affiliation: Molecular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
authors.forename: G M
authors.initials: GM
authors.lastname: Piperno
authors.affiliation: Molecular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.|Immunobiology Division, Center of Molecular Immunology, Havana, Cuba.
authors.forename: A
authors.initials: A
authors.lastname: López-Requena
authors.affiliation: Molecular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Predonzani
authors.affiliation: Immunobiology Division, Center of Molecular Immunology, Havana, Cuba.
authors.forename: D
authors.initials: D
authors.lastname: Dorvignit
authors.affiliation: Immunobiology Division, Center of Molecular Immunology, Havana, Cuba.
authors.forename: M
authors.initials: M
authors.lastname: Labrada
authors.affiliation: Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Zentilin
authors.affiliation: Molecular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
authors.forename: O R
authors.initials: OR
authors.lastname: Burrone
authors.affiliation: Molecular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cesco-Gaspere
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000276:immunology*; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism; D005679:G(M3) Ganglioside / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D005679:G(M3) Ganglioside; D007074:Immunoglobulin G; D011994:Recombinant Proteins