ANTIBODIES TO TRANSCOBALAMIN-II BLOCK IN-VITRO PROLIFERATION OF LEUKEMIC-CELLS

The plasma protein transcobalamin II (TCII) binds and delivers cobalam in (Cbl; vitamin B12) to all cells, which internalize the TCII/Cbl com plex by receptor-mediated endocytosis. congenital deficiency of TCII r esults in intracellular Cbr deficiency, one effect of which is to disr upt DNA synthesis, leading to megaloblastic anemia. We report here an in vitro culture system in which cell growth is dependent on delivery of Cbl to cells by TCII. Recombinant human holo-TCII was shown to supp ort in dose-dependent manner the growth of the human erythroleukemic c ell line K562 and the murine lymphoma cell line BW5147. Free Cbl also supported cell growth; however, at 100- to 1.000-fold higher concentra tions than those effective in the presence of apo-TCII. To determine i f cellular depletion of Cbl could be achieved by interfering with inte ractions between TCII/Cbl and its cell-surface receptor, several monoc lonal antibodies raised against human TCII were studied. Three antibod ies, found to compete for the same binding site on Tell, proved to be effective inhibitors of TCII/Cbl-dependent cell growth. Our results su ggest that monoclonal anti-TCII antibodies that block the function of this protein may prove useful in antitumor therapies. (C) 1997 by The American Society of Hematology.