Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1995-03-16
1997-03-25
Scheiner, Toni R.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435344, 4353441, 436 64, 436813, 5303888, 5303877, 5303913, 5303873, 4241551, 4241741, 4241781, G01N 33574, C07K 1600
Patent
active
056143737
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
The invention relates to a novel tumour antigen and antibodies directed against this antigen, and to their use in diagnosis and therapy of small-cell carcinoma of the lung.
Small-cell carcinoma of the lung is prone to premature metastasis formation. Because of this, a surgical, radiological or chemotherapeutic treatment leads, in a large number of cases, only to a temporary cure. In regressions, therapy resistance against previously effective therapies, such as, for example, irradiation and chemotherapy, occur as a complication. Because of this, it has been considered in future to subject the patient after the conventional treatment of the primary tumour to a specific aftertreatment with antibodies or antibody-conjugated active substances. Labelled antibodies would also be useful for the demonstration of metastases by means of imaging processes or for the examination of tumour tissue by means of histological techniques.
A number of antigens which are expressed by cells of small-cell carcinoma of the lung are known; in accordance with the agreement which has been reached in specialist congresses (First and Second International Workshop on Lung Cancer Antigens; Brit.J. Cancer (1991) 63 (suppl.), pages 10-19; J. Nat Cancer Inst. (1991) 83, 609-612), these are divided into seven groups. Antibodies against these antigens are also known. In animal models, these antibodies have occasionally been employed for the localisation of tumour cells. Important previously known antigens of small-cell carcinoma of the lung are the adhesion molecule of neuronal cells (neural cell adhesion molecule; NCAM), and antigens of the clusters 2 and w4. Further antigens are mucins, the Lewis.sup.y antigen, and the antigens of the ABO blood group system. Antibodies against NCAM and against cluster w4 antigens also bind to leucocytes. Antibodies against cluster 2 antigens also bind to epithelial tissue. Because of this, antibodies of this type are not suitable for systemic applications, as would be desirable for an immunological tumour therapy. A high avidity to the particular antigen is additionally useful so that the antibody is strongly concentrated in the tumour tissue.
Antigens discovered to date having a relative specificity for cells of small-cell carcinoma of the lung and antibodies which are directed against these antigens are not sufficiently selective. They do not permit the reliable detection of cells of small-cell carcinoma of the lung. For methods for the immunological treatment of this disease, the specificity of previously known tumour antigens and avidity of the previously known antibodies are also inadequate. The object of the invention is to provide novel tumour antigens of small-cell carcinoma of the lung, as well as antibodies against these antigens, in order to improve diagnosis and therapy of this cancer. In detail, the object is to provide improved antigens which are dominantly expressed if possible exclusively in tumours in high copy number. Antibodies against antigens of this type should be distinguished by a high avidity.
A novel antigen on the cell surface of cells of small-cell carcinoma of the lung has now been found and characterised which is significantly more specific than previously known antigens for tumour cells, and which in particular does not occur on leucocytes or healthy kidney or lung epithelial cells. The novel antigen is dominantly expressed with a high copy number by cells of small-cell carcinoma of the lung. According to the invention, a monoclonal antibody is provided which binds to the novel antigen specifically and with high avidity.
The invention consequently relates to a murine monoclonal antibody having the designation SEN7, and also a hybridoma cell line having the designation SEN7.2a.4 and the deposit number DSM ACC 2050, which secretes the monoclonal antibody SEN7.
The invention furthermore relates to humanised antibodies having murine hypervariable domains and human framework and constant domains, characterised in that they contain hypervariable domains from the monocl
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Merck Patent Gesellschaft mit beschrankter Haftung
Scheiner Toni R.
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