title: APOBEC3A intratumoral DNA electroporation in mice.
abstract: Human APOBEC3A (A3A) cytidine deaminase shows pro-apoptotic properties resulting from hypermutation of genomic DNA, induction of double-stranded DNA breaks (DSBs) and G1 cell cycle arrest. Given this, we evaluated the antitumor efficacy of A3A by intratumoral electroporation of an A3A expression plasmid. DNA was repeatedly electroporated into B16OVA, B16Luc tumors of C57BL/6J mice as well as the aggressive fibrosarcoma Sarc2 tumor of HLA-A*0201/DRB1*0101 transgenic mice using noninvasive plate electrodes. Intratumoral electroporation of A3A plasmid DNA resulted in regression of ~50% of small B16OVA melanoma tumors that did not rebound in the following 2 months without treatment. Larger or more aggressive tumors escaped regression when so treated. As APOBEC3A was much less efficient in provoking hypermutation and DSBs in B16OVA cells compared with human or quail cells, it is likely that APOBEC3A would be more efficient in a human setting than in a mouse model.
authors.affiliation: Invectys, Pepinière Paris Biotech Santé Cochin, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Kostrzak
authors.affiliation: Molecular Retrovirology Unit, Institut Pasteur, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Caval
authors.affiliation: Invectys, Pepinière Paris Biotech Santé Cochin, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Escande
authors.affiliation: Invectys, Pepinière Paris Biotech Santé Cochin, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Pliquet
authors.affiliation: Invectys, Pepinière Paris Biotech Santé Cochin, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Thalmensi
authors.affiliation: Invectys, Pepinière Paris Biotech Santé Cochin, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Bestetti
authors.affiliation: Invectys, Pepinière Paris Biotech Santé Cochin, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Julithe
authors.affiliation: Human Histopathology and Animal Models, Infection & Epidemiology Department, Institut Pasteur, Paris, France.|Université Paris Descartes, Sorbonne Paris-Cité, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Fiette
authors.affiliation: Invectys, Pepinière Paris Biotech Santé Cochin, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Huet
authors.affiliation: Invectys, Pepinière Paris Biotech Santé Cochin, Paris, France.|Molecular Retrovirology Unit, Institut Pasteur, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Wain-Hobson
authors.affiliation: Invectys, Pepinière Paris Biotech Santé Cochin, Paris, France.|Molecular Retrovirology Unit, Institut Pasteur, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Langlade-Demoyen
mesh_terms: D000818:Animals; D003564:Cytidine Deaminase / Q000235:genetics*; D018274:Electroporation / Q000379:methods*; D005260:Female; D015316:Genetic Therapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D011506:Proteins; C121399:APOBEC3A protein, human; D003564:Cytidine Deaminase