Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1997-09-12
2000-01-18
Reeves, Julie
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435329, 435344, 435183, 5303877, 5303875, 5303888, 5303897, 5303873, 5303913, 5303871, 4241331, 4241371, 4241381, 4241741, 4241551, 4241781, A61K 39395, G01N 3353, C07K 1630
Patent
active
060156805
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
Human lung carcinoma is classified into four principal histological types. That is, lung adenocarcinoma, squamous cell carcinoma, small cell carcinoma and large cell carcinoma. This invention relates to a monoclonal antibody having reactivity with human lung adenocarcinoma, to a glycoprotein antigen recognizable by this antibody and to a detection method and a therapeutic drug of human lung adenocarcinoma in which the monoclonal antibody is used. Also, this invention can be used in the diagnosis and treatment of human lung adenocarcinoma and is applicable to the field of diagnostic drugs and therapeutic drugs of lung adenocarcinoma.
BACKGROUND ART
As a detection method of lung adenocarcinoma, a method has been known in which human lung adenocarcinoma is detected by measuring it using antibodies for carcinoembryonic antigen (CEA) and sialyl SSEA-1 (SLX) known as tumor markers. However, in the diagnostic method which detects these tumor markers, not only the positive ratio on lung adenocarcinoma is 40 to 50% but also they are detected in other tissue type of lung carcinoma, benign lung diseases and other organ cancers including colon cancer, stomach cancer and breast cancer. On the other hand, Maimonis P. et al. (Cancer Res., 50, 6738 (1990)) have reported a monoclonal antibody DF-L1 obtained using a lung adenocarcinoma tissue as the immunogen. However, the antigen which is detected using this antibody is present in sera of patients of not only lung adenocarcinoma but also squamous cell carcinoma, breast cancer and the like.
Thus, the monoclonal antibodies so far developed can hardly be regarded as diagnostic means specific for lung adenocarcinoma and are nor sufficient for screening, definite diagnosis and monitoring of metastasis, recidivation. In addition, lung cancers have different properties in terms of cell proliferation, development and the like, due to different tissue type of each lung cancer. Because of this, the corresponding therapeutic method varies depending on each tissue type. In consequence, it is extremely important to find an antigen and an antibody peculiar to lung adenocarcinoma for the diagnosis of lung adenocarcinoma, and furthermore, for the treatment of lung adenocarcinoma.
DISCLOSURE OF THE INVENTION
Taking the aforementioned actual circumstances into consideration, the inventors of the present invention have conducted intensive studies on lung adenocarcinoma cells and found as the result a high molecular weight glycoprotein which is peculiarly present in the culture broth of an established lung adenocarcinoma cell line Calu-3 (ATCC HTB-55) and in sera of lung adenocarcinoma patients but is hardly detectable in normal human sera, from glycoproteins which are present in the culture broth of the established lung adenocarcinoma cell line Calu-3 (ATCC HTB-55) and can perform cross reaction with the monoclonal antibody DF-L1 prepared by Maimonis P. et al. (Cancer Res., 50, 6738 (1990)). Also, hybridomas TRD-L1, TRD-L2 and TRD-L3 were established using this glycoprotein as the immunogen, and antibodies produced by these cells were obtained. Thereafter, the present invention has been accomplished by further finding that, when said monoclonal antibodies are used, a lung adenocarcinoma-originated antigen can be isolated and said antigen can be measured accurately.
The present invention is as follows.
(1) A monoclonal antibody whose antigen is a secretory glycoprotein specific for human pulmonary adenocarcinoma cell having a molecular weight of 200 kD or more (SDS-PAGE).
(2) The monoclonal antibody according to the above item (1) wherein said glycoprotein reacts with MAA lectin and PNA lectin but not with GNA lectin, SNA lectin and DSA lectin.
(3) The monoclonal antibody according to the above item (1) or (2) wherein its isotype is IgM.
(4) The monoclonal antibody according to any one of the above items (1) to (3) wherein it is produced by a hybridoma cell strain TRD-L1 (original designation FERM P-14878 assigned by National Institute of Bioscience and Human Technology
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Tsuji Kouichi
Uwano Takashi
Yoshida Yoshihiro
Reeves Julie
Terumo Kabushiki Kaisha
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