Targeted Delivery of Immunotoxin by Antibody to Ganglioside GD3: A Novel Drug Delivery Route for Tumor Cells

VANINA TORRES DEMICHELIS; ALDO A. VILCAES; RAMIRO IGLESIAS-BARTOLOME; FERNANDO M. RUGGIERO; JOSE L. DANIOTTI

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2013 vol. 8 p. 1 - 1

1932-6203

angliosides are sialic acid-containing glycolipids expressed on plasma membranes from nearly all vertebrate cells. Theexpression of ganglioside GD3, which plays essential roles in normal brain development, decreases in adults but is upregulated in neuroectodermal and epithelial derived cancers. R24 antibody, directed against ganglioside GD3, is a validatedtumor target which is specifically endocytosed and accumulated in endosomes. Here, we exploit the internalization featureof the R24 antibody for the selective delivery of saporin, a ribosome-inactivating protein, to GD3-expressing cells [human(SK-Mel-28) and mouse (B16) melanoma cells and Chinese hamster ovary (CHO)-K1 cells]. This immunotoxin showeda specific cytotoxicity on tumor cells grew on 2D monolayers, which was further evident by the lack of any effect on GD3-negative cells. To estimate the potential antitumor activity of R24-saporin complex, we also evaluated the effect of theimmunotoxin on the clonogenic growth of SK-Mel-2