Dorvignit D1, García-Martínez L1, Rossin A2, Sosa K1, Viera J3, Hernández T1, Mateo C4, Hueber AO2, Mesa C5, López-Requena A1.[expand title=”Show Affiliations”]
- Immunobiology Direction, Center of Molecular Immunology, Havana, Cuba.
- Institute of Biology Valrose, Nice, France.
- System Biology Direction, Center of Molecular Immunology, Havana, Cuba.
- Innovative Direction, Center of Molecular Immunology, Havana, Cuba.
- Immunobiology Direction, Center of Molecular Immunology, Havana, Cuba. Electronic address: [email protected]
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.
Copyright © 2015 Elsevier GmbH. All rights reserved.Go To Immunobiology.