linical Development geted Delivery of Saporin Toxin by Monoclonal Antibody to Ther Transcobalamin Receptor , TCblR / CD 320 rd

ownload ular uptake of cobalamin (Cbl) occurs by endocytosis of transcobalamin saturated with Cbl by the obalamin receptor (TCblR/CD320). The cell cycle–associated overexpression of this receptor in many cells provides a suitable target for delivering chemotherapeutic drugs and cytotoxic molecules to these hile minimizing the effect on the normal cell population. We have used monoclonal antibodies to the ellular domain of TCblR to deliver saporin-conjugated secondary antibody to various cell lines propain culture. A molar ratio of 2.5:10 nmol/L of primary:secondary antibody concentration was identified lowest concentration needed to produce the optimum cytotoxic effect. The effect was more pronounced cells were seeded at lower density, suggesting lack of cell division in a fraction of the cells at higher y as the likely explanation. Cells in suspension culture, such as K562 and U266 cells, were more severely d than adherent cultures, such as SW48 and KB cells. This differential effect of the anti–TCblR-saporin dy conjugate and the ability of an anti-TCblR antibody to target proliferating cells were further evident virtual lack of any effect on primary skin fibroblasts and minimal effect on bone marrow cells. These by the results indicate that preferential targeting of some cancer cells could be accomplished through the TCblR. Mol Cancer Ther; 9(11); 3033–40. ©2010 AACR.