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医学博士 甲第845号 平成15年1月24日 （埼玉医科大学）
Application of Human Gastric Cancer-reactive Monoclonal Antibodies to Human Lung Cancer
Nobutaka Shimono (Division of Pulmonology, Second Department of Internal Medicine, Saitama Medical School Moroyama, Iruma-gun, Saitama 350-0495, Japan )
Background: Detection and identification of tumor-associated antigens are essential for immunotherapy as well as diagnosis of tumors. Recently mouse monoclonal antibodies (mAbs) against human gastric cancer were raised in our laboratory. Purpose: We asked if these mAbs detect antigens not only of gastric carcinoma cells but also of lung carcinoma cells, and if there are any difference in the localization of tumor-associated antigens among four major histologically different carcinomas of lung. Method: Mice were immunized with human carcinoma cells and normal cells of stomach. Five mAbs (1e2, 3e3, 5b10, 7c4, 7e4) recognizing cell-surface and intracellular molecules of gastric carcinoma cells but not of normal gastric mucosal cells were established by subtractive immunization. Human lung carcinoma cell lines ( 3 squamous cell carcinomas, 2 adeno carcinomas, 3 small cell carcinomas and 6 large cell carcinomas) and two normal human fetal lung fibroblast cell lines were employed. Cell surface and intracellular expression of antigens recognized by mAbs were examined by flow cytometry. In order to examine the intracellular expression, cell surface was treated with Cytofix/Cytoperm® kits to allow mAbs permeabilize into cells. Results: All lung carcinoma cell lines and or lung fibroblast cell lines were positively stained by all five mAbs. Monoclonal Abs were divided into three categories from staining patterns; 1) 3e3 and 7e4 stained both the surface and the inside of both all carcinoma cells and fibroblast cells, 2) 1e2 and 5b10 stained the inside of all carcinoma cells and the surface of carcinoma cells except large cell carcinomas, and 3) 7c4 stained the inside but not the surface of all carcinoma cells. These results revealed that three out of five mAbs raised against human gastric carcinoma cells can also react specifically with human lung carcinoma cells. The findings that two mAbs (1e2, 5b10) reacted with corresponding antigens on the surface and the inside of squamous cell carcinoma, adenocarcinoma and small cell carcinoma, and reacted with an antigen only inside the cells of large cell carcinoma suggest that those mAbs would be diagnostically useful to discriminate large cell carcinoma from other carcinomas. The analysis of corresponding antigens recognized by these three mAbs is needed to testify its usefulness in both the basic and clinical research in the future.
Keywords: Lung cancer, Monoclonal antibody, Large cell carcinoma