INVESTIGADORES
VILCAES Aldo Alejandro
congresos y reuniones científicas
Título:
ENDOCYTOSIS OF ANTIBODY TO GANGLIOSIDE GD3: A POTENTIAL DRUG DELIVERY ROUTE FOR TUMOR CELLS?
Autor/es:
VANINA TORRES DEMICHELIS; VILCAES AA; IGLESIAS-BARTOLOMÉ R; DANIOTTI JL
Lugar:
Potrero de los Funes-San Luis
Reunión:
Congreso; 47 Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2011
Institución organizadora:
SAIB
Resumen:
The expression of ganglioside GD3, which plays essential roles in
normal brain development, decreases in adults but is up regulated in
neuroectoderm-derived cancers, where it enhances malignant
properties. Antibodies to tumor-associated gangliosides are being
used as therapeutic agents. Here, we demonstrated in human (SKMel-
28) and mouse (B16) melanoma cells and hamster ovary cells
(CHO-K1) that the anti GD3 antibody R24 is endocytosed and
accumulated in recycling endosomes, precluding its use as a
naked therapeutic because when internalized it cannot activate
pathways of immune-mediated anticancer activity. However, it
would be possible to exploit the internalization feature for the
selective delivery of cytotoxic agents to GD3+ cancer cells. We have
used antibody R24 to deliver saporin toxin-conjugated secondary
antibody. We incubated cells in a 96-well plate with primary (3-60
nM) and secondary (1-8 nM) antibodies for 72 h, and cell viability
determined. Wells with both antibody showed a decreasing of 70,
40 and 30% of cell viability in CHO-K1, SK-Mel-28 and B16 cells,
respectively. The effect of the R24-saporin antibody conjugate was
further evident by the lack of any effect on GD3-negative cells.
Similar results were obtained using biotin-R24 coupled to
streptavidin-saporin in SK-Mel-28 cells. The data suggest that GD3
may be a viable target for drug delivery for tumor cells.
used antibody R24 to deliver saporin toxin-conjugated secondary
antibody. We incubated cells in a 96-well plate with primary (3-60
nM) and secondary (1-8 nM) antibodies for 72 h, and cell viability
determined. Wells with both antibody showed a decreasing of 70,
40 and 30% of cell viability in CHO-K1, SK-Mel-28 and B16 cells,
respectively. The effect of the R24-saporin antibody conjugate was
further evident by the lack of any effect on GD3-negative cells.
Similar results were obtained using biotin-R24 coupled to
streptavidin-saporin in SK-Mel-28 cells. The data suggest that GD3
may be a viable target for drug delivery for tumor cells.
+ cancer cells. We have
used antibody R24 to deliver saporin toxin-conjugated secondary
antibody. We incubated cells in a 96-well plate with primary (3-60
nM) and secondary (1-8 nM) antibodies for 72 h, and cell viability
determined. Wells with both antibody showed a decreasing of 70,
40 and 30% of cell viability in CHO-K1, SK-Mel-28 and B16 cells,
respectively. The effect of the R24-saporin antibody conjugate was
further evident by the lack of any effect on GD3-negative cells.
Similar results were obtained using biotin-R24 coupled to
streptavidin-saporin in SK-Mel-28 cells. The data suggest that GD3
may be a viable target for drug delivery for tumor cells.