Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
1999-02-22
2001-01-23
Stucker, Jeffrey (Department: 1648)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C435S004000, C435S003000, C435S007200, C435S007210, C435S007230, C435S007700, C435S007720, C435S007800, C435S007900, C435S007920, C435S007930, C435S007940, C435S028000
Reexamination Certificate
active
06177255
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention concerns a method for detecting a hormone or antihormone resistance in tumours. The invention is intended for use in medicine, biology and pharmaceutical industry.
Tumours in organs depending on hormones such as in the breast and ovaries are tumour diseases met most frequently in women in industrialized countries. Thus, in about 12% of the female population breast cancer is diagnosed, with the peak of sickening being between the 4
th
and 6
th
decade of life. 3.5% of women die of it (Harris et al., New England J Med 327: 319-328, 1992).
Depending on the stage at which breast cancer is diagnosed the chances of recovery are between 30 and 70%. As about ⅔ of the tumours detected have hormone receptors these patients are given hormone preparations as primary medication. They are to competitively displace the natural ligand (oestrogen) from the receptor, thus affecting the growth of the tumours caused by hormones. Tamoxifen, a non-steroidal antioestrogen, is most frequently used for treating mammary carcinomas with the adjuvant use to prevent the development of metastases, yet also the prophylactic use for patients with a family-connected risk (Harris et al., New England J Med 327: 473-480, 1992).
It is known that about only half of the hormone receptor-positive patients respond to a tamoxifen therapy. This raises questions relating to the principle action of antioestrogens which, for the time being, are still largely unclarified. Thus, Berthois et al. (Molecular and cellular Endocrinology 99: 259-268, 1994) described that the immune reactivity of oestroqen receptors to an antibody will increase if oestradiol or tamoxifen are added in a cytosole test. The authors discuss a change of conformation of the oestrogen receptor by an in vitro interaction with hormones and anti-hormones as a potential mechanism for an apparent increase of the positions for the epitope binding.
Though tamoxifen is comparatively well-tolerated also in long-term use its possible cancerogenic potential has been discussed recently (Williams et al., Eur J Cancer Prev 1: 386-387, 1992).
SUMMARY OF THE INVENTION
The invention is aimed at improving the use of antihormones for the therapy of tumours in order to avoid unnecessary therapies as far as possible. Its aim is to develop a method which allows to predict the response of a tumour before applying a respective antihormone therapy.
Starting point of the invention is the surprising finding that the immune reactivity of sensitive and at resistant tumours differs given specific conditions of reaction. If hormone receptors contained in the tumour are bound to an antibody, in the case of sensitive tumours, their inmmune reactivity is increased by adding respective hormones or antihormones, however not in the case of resistant tumours. That means, the positions of epitope binding are apparently increased only in the case of sensitive tumours.
This effect has been used for designing the method according to the invention wherein an antihormone receptor antibody bound to a solid phase is incubated with cytosole prepared of the tumour tissue under investigation, the liquid is subsequently removed and adding the appropriate hormones or antihormones a repeated incubation i s performed and subsequently a second enzyme-labelled antibody is added, the colour reaction is measured and the value determined for the immune reaction is compared with the control value determined in the same way, but without incubation with the appropriate hormones or antihormones.
In this description n we understand by hormones oestrogens (such as 17&bgr;-oestradiol), progesterone or androgen, by antihormones antioestroqens (such as tanoxifen or 4-hydroxy-tamoxifen), antiprogestins or antiandrogens (such as cyproteronacetate).
REFERENCES:
patent: 5292638 (1994-03-01), Benz et al.
patent: 0 129 669 (1985-02-01), None
Y. Berthois, et al.; Agonist-antagonist activity of anti-estrogens in the human breast cancer cell line MCF-7: an hypothesis for the interaction with a site distinct from the estrogen binding site; Molecular and Cellular Endocrinology, 99(1994) pp. 259-268.
A. Wakeling; Are breast tumours resistant to tamoxifen also resistant to pure antioestrogens?; J. Steriod Biochem. Molec. Biol. vol. 47, No. 1 6, pp. 107-114 1993.
G. Williams et al.; Long-term prophylactic use of tamoxifen: is it safe?; European Journal of Cancer Prevention, vol. 1 1992 pp. 386-387.
J. Harris et al.; Breast Cancer (Third of Three Parts); New England Journal of Medicine, vol. 327, No. 7 Aug. 13, 1992 pp. 473-480.
J. Harris et al.; Breast Cancer (First of Three Parts); New England Journal of Medicine, vol. 327, No. 5 Jul. 30, 1992 pp. 319-328.
H. Naundorf et al.; Establishment and characterization of a new human oestradiol-and progesterone-receptor-positive mammary carcinoma serially transplantable in nude mice; J. Cancer Res.Clin.Oncol. 1992 119: pp. 35-40.
Berthois et al.; Agonist-antagonist activity of ani-estrogens in the human breast cancer .... ; Molecular and Cellular Endocrinology; vol. 99; pp. 259-268, 1994.
Harlow et al.; Antibodies a laboratory manual; pp. 578-581, 1988.
Lippman et al.; Current concepts in cancer- receptors in breast cancer; The New England journal of Medicine; vol. 299, No. 17; pp. 930-933, Oct. 1978.
Becker Michael
Fichtner Iduna
Naundorf Helga
Neumann Claudia
Max-Delbr{umlaut over (u)}ck-Centrum f{umlaut over (u)}r Molekul
Nelson Brett
Norris McLaughlin & Marcus P.A.
Stucker Jeffrey
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