Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of... – Animal cell – per se – expressing immunoglobulin – antibody – or...
Patent
1995-02-23
1997-03-11
Eisenschenk, Frank C.
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
Animal cell, per se, expressing immunoglobulin, antibody, or...
5303882, C07K 1628, C12N 500
Patent
active
056100582
DESCRIPTION:
BRIEF SUMMARY
The invention relates to a monoclonal antibody with a unique binding pattern, and the antigen to which the monoclonal antibody binds.
Cytotrophoblast are a cell type unique to the placenta and fetal membranes. In early pregnancy, the extra-villous cytotrophoblast of the cell columns infiltrate the maternal decidua lining the uterus and anchor the placenta [Boyd & Hamilton, 1970], later also invading the maternal spiral arteries as part of a process which allows the hugely increased uteroplacental blood flow required for successful pregnancy [Pijnenborg et al., 1980]. The villous cytotrophoblast covering the chorionic villi fuse and differentiate to form the syncytiotrophoblast which is the major site of exchange of nutrients and waste products between the fetus and the maternal circulation. In the fetal membranes, the extra-villous trophoblast of the chorion are also in direct contact with the maternal decidua [Boyd & Hamilton, 1970].
Trophoblast are known to be heterogeneous, both in function and morphology, but the various trophoblast subsets are poorly defined. Anti-trophoblast antibodies with different specificities are useful for characterising these subsets.
Another use for anti-trophoblast antibodies which may be of significant value commercially is contraception. Monoclonal antibodies could provide a reliable and convenient new method of contraception free of side-effects.
The present invention provides a monoclonal antibody, designated antibody X, raised against a highly purified population of first trimester human cytotrophoblast taken from cell islands, small clumps of extra-villous cytotrophoblast partially covered by syncytiotrophoblast, which are found mainly in first trimester tissue.
In first trimester tissue, antibody X binds to cell island and the interstitial trophoblast invading the maternal decidua. In the second trimester and at term, the antibody labels a subset of cytotrophoblast in the amniochorion. Antibody X does not react with syncytiotrophoblast or villous cytotrophoblast in first trimester placenta, or with term syncytiotrophoblast. The antigen detected by antibody X is specific for cytotrophoblast, and is not present on amniotic epithelium, decidual cells, or villous stromal cells in first trimester or at term. Antibody X does not bind to any normal adult human tissues tested and is not present on breast or cervical carcinoma cells. In relation to other anti-trophoblast antibodies, antibody X defines a unique subset of extra-villous trophoblast, which in the first trimester corresponds to the most invasive forms.
As part of the World Health Organisation 3rd Trophoblast Antigen and Monoclonal Antibody Workshop, 30th Aug. 1992, Rome, Italy, 29 different monoclonal antibodies were tested extensively by participating laboratories for their binding specificities. The final report shows a consensus finding that the monoclonal antibody of the present invention (identified as T77 in the study) is the only human monoclonal antibody with specificity for extra-villous trophoblast and no cross-reactivity with other tissues.
The monoclonal antibody BC-1 of Loke et al. [1992] is also directed at a cell surface antigen expressed by extra-villous cytotrophoblast, but is shown in the WHO Workshop (T93) to cross-react with various human tissues, including other placental cell types.
Further monoclonal antibodies investigated included several from the laboratory of Mueller et al, none of which showed the unique characteristics of monoclonal antibody X. A paper by Mueller et al. [1987] discusses monoclonal antibodies to trophoblast and describes the interest in identifying surface membrane antigens on extra-villous cytotrophoblast cells. There is no disclosure of antibodies with the binding specificity of antibody X, or of the antigen against which antibody X is directed.
The invention also includes a cell line known as cell line X which produces the claimed antibody. Cell line X was deposited under the Budapest Treaty, at the European Collection of Animal Cell Cultures, Porton Down, Salisbury,
REFERENCES:
Goding, Monoclonal Antibodies Principles & Practice, 1986, pp. 125-132, 219-240 Sigma Catalog, pp. 186-187, 193, 1990.
Wild, "Teopholdast Cell Surface Receptors," in Biology of Trophoblast, Loke & Whyte, eds., 1983, Elsevier Science Publishers, pp. 473-479.
Shorter, The Isolation & Characterization of Human Cytotrophoblast pp. 68-69, 212-214, 1989.
Shorter et al., Placenta, vol. 12, No. 4, pp. 434-435 (Jul. 1991).
Mueller et al., The Histochemical Journal, vol. 19, pp. 288-296 (1987).
Loke et al., American Journal of Reproductive Immunology, vol. 27, No. 1/2 (Jan.-Mar. 1992).
Shorter, Dissertation Abstracts International, vol. 52/01-B, p. 170 (1989) (Dialog printout).
Ferry Bernadette L.
Redman Christopher W. G.
Sargent Ian L.
Shorter Simon C.
Starkey Phyllis M.
Eisenschenk Frank C.
Isis Innovation Limited
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