Antibody-directed cytotoxic agents: use of monoclonal antibody to direct the action of toxin A chains to colorectal carcinoma cells.

Gilliland, D. Gray; Steplewski, Zenon; Collier, R. John; Mitchell, Kenneth F.; Chang, Tong; Koprowski, Hilary

doi:10.1073/pnas.77.8.4539

Cited by 218 publications

(59 citation statements)

References 36 publications

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“…There is considerable evidence suggesting that the primary role of transferrin as a growth factor in vitro is to provide iron (23,(38)(39)(40)(41)(42). Monoclonal antibodies against T-cell differentiation antigens also have been used in attempts to eliminate tumor cells by immunological effector mechanisms (43)(44)(45)(46) (1982) …”

Section: Discussionmentioning

confidence: 99%

Monoclonal antibody to transferrin receptor blocks transferrin binding and inhibits human tumor cell growth in vitro.

Trowbridge¹,

Lopez²

1982

Proc. Natl. Acad. Sci. U.S.A.

295

143

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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 jtg 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.Iron plays an important role in cell growth and metabolism (1). Key reactions in energy metabolism and DNA synthesis are catalyzed by iron-containing enzymes, and it has been known for several years that transferrin, the major serum iron-transport protein, is an obligatory growth factor for cells growing in vitro (2-11). More recently, it has become apparent that cell surface receptors for transferrin are not only found in abundance on maturing erythroid cells and placental membranes but are expressed on proliferating cells in vitro and in vivo (12-16).We and others have obtained monoclonal antibodies that react with the human cell surface receptor for transferrin and confirmed that the expression of transferrin receptors is regulated by the growth state ofthe cells (17)(18)(19)(20)(21)(22). Although the antitransferrin-receptor monoclonal antibody, which we obtained and designated B3/25, inhibits the growth of a human melanoma cell line in nude mice (23), it does not interfere with either transferrin binding or cell growth in vitro. In this paper, we report the identification ofanother murine monoclonal antibody against-the human transferrin receptor that blocks transferrin binding and show that this antibody blocks the growth of a human T leukemic cell line in vitro.MATERIALS AND METHODS Cell Lines. CCRF-CEM, a human thymus-derived (T) leukemic cell line (24), was grown in RPMI 1640 medium supplemented with 10% horse serumn. BW5147, a murine T lymphoma cell line (25) was grown in Dulbecco's modified Eagle's medium supplemented with 10% horse serum.Monoclonal Antibodies. Monoclonal antibodies B3/25 and T56/14 directed against the human transferrin ...

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Section: Discussionmentioning

confidence: 99%

Monoclonal antibody to transferrin receptor blocks transferrin binding and inhibits human tumor cell growth in vitro.

Trowbridge¹,

Lopez²

1982

Proc. Natl. Acad. Sci. U.S.A.

295

143

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“…The targeting of drugs or toxins to tumor cells by specific antibodies has long been a topic of interest [15]. Using monoclonal antibodies generated by immunizations with neoplastic cells, Trowbridge and Omary [8] and Sutherland and colleagues [9] identified the transferrin receptor as a major cell surface protein in proliferating cells.…”

Section: Tf and Tfr Conjugates For Improved Uptake Into Cellsmentioning

confidence: 99%

Delivery of drugs, proteins and genes into cells using transferrin as a ligand for receptor-mediated endocytosis

Wagner

Curiel

Cotten

1994

Advanced Drug Delivery Reviews

259

128

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“…A number of research groups are examining closely the part that anti-idiotype antibodies may play in the therapy of lymphoma used alone , with attached drugs and toxins (Gilliland et al, 1980;Embleton et al, 1983), or carrying cellsterilising amounts of radionuclides (Larsen et al, 1983). In B cell lymphoma/leukaemia a major problem can arise in some patients from large quantities of circulating idiotype which can effectively block the entry of the therapeutic antibody into the tumour infiltrated tissues .…”

Section: Cytogenetic Preparationsmentioning

confidence: 99%

Characterisation of a new murine B cell lymphoma

Cobb¹,

Glennie²,

McBride³

et al. 1986

Br J Cancer

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The characterisation of a new murine B cell lymphoma, A31, is described. Histopathological examination of passaged tumour indicates that initial infiltration occurs in the spleen, lymph nodes, Peyer's patches and liver, while in the terminal phase the bone marrow, gonads and occasionally the central nervous system become involved. The terminal spread is coincidental with the leukaemic phase in the tumour. The tumour cells show typical B cell characteristics in vitro. These include surface immunoglobulin (Ig) of mu, kappa isotype, surface Ia, Thy-1 negativity and an increased uptake of tritiated thymidine following incubation with lipopolysaccharide. A31 cells secrete low levels of IgM into the tissue culture fluid. Short-term culture produced only 100 ng IgM per 10(7) cells over 8 h and no tumour-associated monoclonal band could be detected in the serum of tumour-bearing mice. Chromosomal karyotypes of A31 cells gave model numbers 2n=40 normal, and 2n=41, with partial trisomy of chromosome 2, and trisomy of 17. There was loss of a chromosome 6 and the Y chromosome, together with the translocation of part of an 11 to one of the two unidentified marker chromosomes. The responses of lymphoma-bearing mice to therapeutic levels of cyclophosphamide and vincristine sulphate and also to whole body X-radiation are illustrated. This tumour may help in unravelling the complex biology of B cell lymphoma and because of its low level of Ig secretion, be of particular value in experimental immunotherapy. Images Figure 1 Figure 5

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Antibody-directed cytotoxic agents: use of monoclonal antibody to direct the action of toxin A chains to colorectal carcinoma cells.

Cited by 218 publications

References 36 publications

Monoclonal antibody to transferrin receptor blocks transferrin binding and inhibits human tumor cell growth in vitro.

Monoclonal antibody to transferrin receptor blocks transferrin binding and inhibits human tumor cell growth in vitro.

Delivery of drugs, proteins and genes into cells using transferrin as a ligand for receptor-mediated endocytosis

Characterisation of a new murine B cell lymphoma

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