Saporin Conjugated Monoclonal Antibody to the Transcobalamin Receptor TCblR/CD320 Is Effective in Targeting and Destroying Cancer Cells

Abstract

Cobalamin uptake into cells is mediated by the CD 320 receptor for transcobalamin-bound cobalamin. Optimum rec e p tor expression is associated with proliferating cells and therefore, in many cancers this receptor expression is up regu lated. 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 2.5 nM 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 CD 320 were spared while tumor cell lines with higher CD 320 expression were destroyed. Targeting the path way for cellular uptake of vitamin B 12 via the CD 320 receptor with toxin-antibody conjugates appears to be a viable treatment strategy for certain cancers that over express es this receptor.