Characterizing monoclonal antibodies to antigenic domains of TCblR/CD320, the receptor for cellular uptake of transcobalamin-bound cobalamin

Abstract

Monoclonal antibodies (mAbs) were generated to the extracellular domain of transcobalamin receptor (TCblR) and used to identify the regions of the receptor protein involved in antibody binding. Based on the effect of transcobalamin bound cobalamin (TC-Cbl) on antibody binding, this study identified both blocking and binding antibodies. Both types of antibodies bind apo as well as holo receptors, whereas the blocking antibody when bound to the apo receptor prevents the binding and cellular uptake of TC-Cbl. Binding of these antibodies to truncated receptor constructs has identified the peptide domains of the receptor involved in antibody binding. These antibodies have potential utility in blocking cellular uptake of Cbl and delivery of drugs via TCblR, which is over-expressed in many cancers.

Keywords::

• Transcobalamin
• receptor
• TCblR/CD320
• monoclonal antibodies
• cobalamin
• vitamin B12.

Acknowledgements

This work is supported by NIH grant R01DK064732 and by KYTO Biopharma, Toronto, CA.

Declaration of interest: Two of the authors (EVQ and JMS) are coinventors in a patent filing WO 2007/117657 A2 on the use of this receptor as a target in cancer therapy filed by the Research Foundation of the State University of New York.