Cobalamin uptake into cells is
mediated by the CD320receptor for transcobalamin-bound
cobalamin. Optimum receptor expression is associated with
proliferating cells and therefore, in many cancers this receptor expression is
up regulated. Delivering
drugs or toxins via this receptor provides increased targeting to cancer cells
while minimizing toxicity to the normal tissues. Saporin conjugated monoclonal
antibodies to the extracellular domain of TCblR were effectively internalized
to deliver a toxic dose of Saporin to some cancer cell lines propagating in
culture. Antibody concentration of 2.5nM was effective in producing optimum inhibition of cell proliferation.
The cytotoxic effect of mAb-Saporin appears to be dictated primarily by the
level of receptor expression and therefore normal primary cells expressing low
levels of CD320 were spared while
tumor cell lines with higher CD320
expression were destroyed. Targeting the pathway for cellular uptake of vitamin B12 via the CD320 receptor with
toxin-antibody conjugates appears to be a viable treatment strategy for certain
cancers that over expresses this receptor.
Cite this paper
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