title: Antitumor and cytotoxic properties of a humanized antibody specific for the GM3(Neu5Gc) ganglioside.
abstract: Gangliosides are sialic acid-bearing glycosphingolipids expressed on all mammalian cell membranes, and participate in several cellular processes. During malignant transformation their expression changes, both at the quantitative and qualitative levels. Of particular interest is the overexpression by tumor cells of Neu5Gc-gangliosides, which are absent, or detected in trace amounts, in human normal cells. The GM3(Neu5Gc) ganglioside in particular has been detected in many human tumors, and it is considered one of the few tumor specific antigen. We previously demonstrated that a humanized antibody specific for this molecule, named 14F7hT, retained the binding and cytotoxic properties of the mouse antibody. In this work, we confirm that 14F7hT exerts a non-apoptotic cell death mechanism in vitro and shows its potent in vivo antitumor activity on a solid mouse myeloma model. Also, we demonstrate, in contrast to the murine counterpart, the capacity of this antibody to induce antibody-dependent cell-mediated cytotoxicity using human effector cells, which increases its potential for the treatment of GM3(Neu5Gc)-expressing human tumors.
authors.affiliation: Immunobiology Direction, Center of Molecular Immunology, Havana, Cuba.
authors.forename: Denise
authors.initials: D
authors.lastname: Dorvignit
authors.affiliation: Immunobiology Direction, Center of Molecular Immunology, Havana, Cuba.
authors.forename: Liliana
authors.initials: L
authors.lastname: García-Martínez
authors.affiliation: Institute of Biology Valrose, Nice, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Rossin
authors.affiliation: Immunobiology Direction, Center of Molecular Immunology, Havana, Cuba.
authors.forename: Katya
authors.initials: K
authors.lastname: Sosa
authors.affiliation: System Biology Direction, Center of Molecular Immunology, Havana, Cuba.
authors.forename: Justo
authors.initials: J
authors.lastname: Viera
authors.affiliation: Immunobiology Direction, Center of Molecular Immunology, Havana, Cuba.
authors.forename: Tays
authors.initials: T
authors.lastname: Hernández
authors.affiliation: Innovative Direction, Center of Molecular Immunology, Havana, Cuba.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mateo
authors.affiliation: Institute of Biology Valrose, Nice, France.
authors.forename: Anne-Odile
authors.initials: AO
authors.lastname: Hueber
authors.affiliation: Immunobiology Direction, Center of Molecular Immunology, Havana, Cuba. Electronic address: circe@cim.sld.cu.
authors.forename: Circe
authors.initials: C
authors.lastname: Mesa
authors.affiliation: Immunobiology Direction, Center of Molecular Immunology, Havana, Cuba.
authors.forename: Alejandro
authors.initials: A
authors.lastname: López-Requena
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000494:pharmacology*; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005679:G(M3) Ganglioside / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D064596:Isografts; D051379:Mice; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D005679:G(M3) Ganglioside
keywords: Antibody dependent cell-mediated cytotoxicity; Antitumor effect; Apoptosis; GM3(Neu5Gc) ganglioside; Necrosis