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

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

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2013 vol. 8 p. 55304 - 55317

1932-6203

Gangliosides 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-28 and CHO-K1GD3+cells cultured in attachment-free conditions. Adrastic growth inhibition (.80?90%) of the cell colonies was reached after 3 days of immunotoxin treatment. By thecontrary, colonies continue to growth at the same concentration of the immuntoxin, but in the absence of R24 antibody, orin the absence of both immunotoxin and R24, undoubtedly indicating the specificity of the effect observed. Thus, theganglioside GD3 emerge as a novel and attractive class of cell surface molecule for targeted delivery of cytotoxic agentsand, therefore, provides a rationale for future therapeutic intervention in cancer