title: 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 theCD320 receptor 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 2.5 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 ofCD320 were spared while tumor cell lines with higherCD320 expression were destroyed. Targeting the pathway for cellular uptake of vitamin B12via theCD320 receptor with toxin-antibody conjugates appears to be a viable treatment strategy for certain cancers that over expresses this receptor.
authors: Department of Medicine, SUNY-Downstate Medical Center, Brooklyn, USA ; Department Cell Biology, SUNY-Downstate Medical Center, Brooklyn, USA.
authors: Edward V
authors: EV
authors: Quadros
authors: Department of Medicine, SUNY-Downstate Medical Center, Brooklyn, USA.
authors: Yasumi
authors: Y
authors: Nakayama
authors: Department of Medicine, SUNY-Downstate Medical Center, Brooklyn, USA.
authors: Jeffrey M
authors: JM
authors: Sequeira
keywords: CD320 Gene; Cancer; Cobalamin; Toxin; Transcobalamin Receptor