Biomedical subjects

A Furuya

Publications and source records attributed to A Furuya.

76 records · Page 5Linked to original sources

PubMedDate not supplied

Application of anti-sialyl Lea monoclonal antibody, KM231, for immunotherapy of cancer.

A mouse monoclonal antibody (MoAb), KM231 raised against human gastric cancer was found to recognize sialyl Lea -epitope expressed on glycoprotein and glycolipid with high affinity. KM231 reacted with many human gastrointestinal cancer tissues and could detect the antigen shed in sera of cancer patients. The present study was designed to evaluate competence of KM231 for immunotherapy of cancer. We first confirmed that KM231 could probe the cancer cells in vivo by injecting biotinylated KM231 into nude mice bearing human colorectal carcinoma cell, SW1116. Light- and electron-microscopic examination showed that the MoAb was localized in the tumor tissues and bound to the plasma membrane and cytoplasmic endosomes. Imaging studies with 125I-labeled KM231 revealed specific localization of the antibody in SW1116 tumors transplanted into nude mice. From Scatchard analysis of KM231 binding, the number of KM231 molecules bound to per SW1116 cell was calculated approximately 1.9 x 10(6) and the association constant was 1.3 x 10(8) liter/mol. We made KM231-ricin A chain immunotoxin for evaluating the tumoricidal effect of KM231. The immunotoxin exerted strong cytotoxicity toward sialyl Lea-expressing tumor cells specifically in vitro, but not toward sialyl Lea non-expressing cells. The in vivo tumoricidal effect of the immunotoxin was examined on ascites and subcutaneous xenograft tumors in nude mice. Three intraperitoneal injections of the immunotoxin (1.6 x 10(-6) mol) into nude mice bearing SW1116 ascites tumor resulted in extension of survival by 204% compared with controls. Further, repeated intraperitoneal administration of the immunotoxin (1.4 - 2 x 10(-6) mol) significantly inhibited the growth of established subcutaneous tumor (ratio of tumor inhibition = 0.7 - 0.54). These results indicated that KM231 has the ability to probe sialyl Lea-expressing tumor cells in vivo with high efficiency and to become tumoricidal drug when it conjugated with cytotoxic reagents like ricin A chain.

Animals↗

PubMedDate not supplied

Detailed characterization of reactivities of anti-gastric cancer monoclonal antibodies to carbohydrate antigen.

Four murine monoclonal antibodies (MoAbs), KM191, KM206, KM230 and KM231, raised against gastric cancer exhibited very similar reactivities to human carcinoma cells, whereas their abilities in probing the antigen shed from the cancer cells were quite different. We found in this study that the four MoAbs reacted immunologically with the same monosialo gangliosides derived from a gastric cancer cell line by two-dimensional high performance thin-layer chromatography. When the reactivities of the MoAbs to a number of purified gangliosides or oligosaccharides were examined, the carbohydrate structure of the antigen was determined as sialyl Lea. KM231 exhibited the highest binding avidity to the oligosaccharide and the ganglioside among the four MoAbs. In a comparative study of KM231 and NS19-9, which is a widely used sialyl Lea-reactive MoAb, KM231 bound to the oligosaccharide with higher affinity and detected the antigen in tissue sections with higher sensitivity. In addition, KM231 could detect a small amount of the antigen ganglioside in human gastric normal and cancerous mucosa and in gastric cancer cell lines by HPTLC-immunostaining.

Animals↗

PubMedDate not supplied

Comparative studies on monoclonal antibodies raised against human gastric cancer for application to serum diagnosis of cancer.

Four murine MoAbs, KM191(IgM), KM206(IgM), KM230(IgG1) and KM231(IgG1), against human gastric cancer were generated using mice which underwent tolerance treatment to stomach tissues. They exhibited very similar high reactivities to stomach adenocarcinoma cells and low reactivities to normal cells in both membrane binding assay and immunohistochemical analysis. Their antigens were neuraminidase and protease sensitive and existed as macromolecules (1,000Kd) in body fluids. Binding of each antibody was inhibited by the others and KM231 showed the highest binding avidity. When they were used to detect the antigens shed in ascitic fluids and pleural effusions of cancer patients, KM231 allowed the most efficient detection of the antigen. The above results indicated that the four MoAbs bound to closely related epitopes on the same antigen and that the nature of its high binding avidity enabled KM231 to show the greatest efficiency in the detection of the antigen in body fluids. KM231 was applied to serum diagnosis and gave high positive percentages in pancreatic cancer(86%), hepatocarcinoma(87%), gall bladder cancer(50%), and gastric cancer(34%), whereas in healthy persons (0%) and benign diseases except for hepatitis(29%) the percentages were low. KM231 was similar to NS19-9, but quite different from NS19-9 in the high positive percentages of hepatocarcinoma in serum diagnosis.

Adenocarcinoma↗

PubMedDate not supplied

Advantage of cocktail-use of two anti-tumor monoclonal antibodies, KM-93 and KM-231, in serum diagnosis of cancer.

Two mouse monoclonal antibodies (MoAbs), KM-93 raised against human lung adenocarcinoma and KM-231 raised against human gastric cancer, were useful in serum diagnosis of several human cancer. KM-93 and KM-231 recognize sialyl Lex epitope and sialyl Lea epitope, respectively, expressed on glycoprotein and glycolipid. We established a new "cocktail" sandwich enzyme-linked immunosorbent assay system using the two MoAbs and the advantage of this assay system, which can simultaneously detect sialyl Lex and sialyl Lea antigens, is assessed in the present study. The new assay system is composed of a mixture of KM-93 and KM-231 as 1st antibodies and a mixture of biotinylated two MoAbs as 2nd antibodies. We evaluated the concentration of MoAbs and optimized it to gain high cancer-positivity. This assay system covered sialyl Lex positive and/or sialyl Lea-positive sera and gave a high rate of positive results in lung adenocarcinoma (62.3%), gastric cancer (32.5%), colon cancer (37.5%), pancreatic cancer (83.3%), bile duct and gall bladder cancer (66.7%) and hepatoma (76.9%), whereas positive results in healthy adults remained low. Positive results in benign diseases of lung (12.5%), pancreas (10.8%), gall bladder and bile duct (9.1%) were very low, but were higher in liver cirrhosis (33.3%), hepatitis and liver injury (34.8%). Simultaneous detection of two carbohydrate antigens, sialyl Lex and sialyl Lea was clearly superior to single detection.

Adenocarcinoma↗