Detection of a novel lung adenocarcinoma--associated serum antigen defined by two monoclonal antibodies, KM 432 and KM 227.

Two monoclonal antibodies, KM227 (IgM) and KM432 (IgG1), were established by immunizing mice with the crude membrane fraction of lung squamous cell carcinoma and the high-molecular-weight antigen in pleural perfusion from patients with lung adenocarcinoma, respectively. They were found to recognize the carbohydrate epitope and the peptide epitope on the antigens, respectively. Both KM227 and KM432 bound to the serum antigens associated with lung adenocarcinoma and lung benign diseases. A double determinant assay in which KM432 was used as 1st antibody and biotinylated KM227 was used as 2nd antibody selectively detected the antigen, designated KA432/227, elevated in sera from patients with lung adenocarcinoma. The molecular weight of KA432/227 in pleural perfusion from patients with lung adenocarcinoma was estimated to be more than 900 kD by the gel filtration chromatography. Serum with a high KA432/227 level was most frequently found in lung adenocarcinoma (47.8%), and occasionally found in lung squamous cell carcinoma (23.1%), lung large cell carcinoma (22.2%), pancreatic carcinoma (20.0%) and carcinoma of the bile-duct and the gall bladder (25.0%). In contrast, positive percentages in benign diseases and healthy adults were very low (0 to 7.7%). No significant correlation was found between the serum level of KA432/227 and other lung adenocarcinoma associated antigens, such as sialyl Le(x). Combined detection of KA432/227 and sialyl Le(x) antigen elevated the positive percentages in lung adenocarcinoma (67.2%).