Monoclonal antibody to transferrin receptor blocks transferrin binding and inhibits human tumor cell growth in vitro.
A murine hybridoma has been obtained that produces a monoclonal antibody against the human transferrin receptor. In contrast to previously characterized monoclonal antibodies that recognize the transferrin receptor, this antibody, designated 42/6, blocks the binding of transferrin to its receptor and inhibits the growth of the human T leukemic cell line, CCRF-CEM, in vitro. Inhibition of cell growth was dose dependent, and as little as 2.5 micrograms of purified antibody per ml had a detectable effect, even though transferrin was present in the tissue culture medium in large molar excess. Cells grown in the presence of antibody for 7 days accumulated in S phase of the cell cycle. The addition of iron to antibody-treated cultures in the form of ferric complexes or ferrous sulfate did not overcome the growth inhibitory effects of the anti-transferrin-receptor antibodies. This result suggests that either transferrin is the only means by which CCRF-CEM leukemic cells can be provided with sufficient iron in vitro or that other factors in addition to iron starvation are involved in the antibody-mediated growth inhibition. The inhibition of cell growth by 42/6 monoclonal antibody suggests that monoclonal antibodies against proliferation-associated cell surface antigens, such as the transferrin receptor, may be useful pharmacological reagents to modify cell growth in vitro.
D000911:Antibodies, Monoclonal / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D005290:Ferric Compounds / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D006801:Humans; D007399:Interphase; D007938:Leukemia / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D011990:Receptors, Transferrin; D013601:T-Lymphocytes; D014168:Transferrin / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D005290:Ferric Compounds; D005296:Ferrous Compounds; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D014168:Transferrin; C020748:ferrous sulfate