A monoclonal antibody, KM10 reactive with human gastrointestinal cancer and its application for immunotherapy.
A monoclonal antibody, KM10 (IgG1) was produced by fusing spleen cells from a human gastric cancer cell (MKN45)-primed BALB/c mouse with the murine myeloma cell line X63-Ag8-653. The antibody reacted strongly with the plasma membrane of human gastrointestinal carcinoma. Sections of the malignant and benign tissues were tested with immunoperoxidase. All of 10 (100%) large intestinal cancers, 26 of 31 (84%) gastric cancers, 5 of 7 (71%) pancreatic cancers and all of 3 (100%) ampullary cancers reacted positively. Moderate or weak reactivity was observed with normal human tissues, hepatoma and carcinomas of mammary, thyroid and adrenal glands. According to a study of the distribution of 125I-labeled KM10 in nude mice bearing human gastric cancer, KM10 selectively localized in tumor tissue rather than normal tissue. Whole body autoradiography also supported such a selective distribution. Destruction of antigenic properties by pronase digestion demonstrated its protein nature and by Western blot analysis, it was identified as a protein with an Mr of 180-200 kd. KM10-adriamycin (ADM) conjugate was prepared via an oxidized dextran bridge and this immunoconjugate retained the binding activity against human gastric cancer. MKN45 cells were inoculated subcutaneously into athymic mice and intravenous treatment was begun when the tumor became measurable. A dose-dependent antitumor activity was observed in vivo with KM10-ADM conjugate, while this conjugate was less toxic than free ADM.
Ohyanagi
H
H
First Department of Surgery, Kobe University School of Medicine.
Ishida
H
H
Ishida
T
T
Soyama
N
N
Yamamoto
M
M
Okumura
S
S
Kano
Y
Y
Ueda
Y
Y
Saitoh
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000032:analysis; D015153:Blotting, Western; D002272:Carcinoembryonic Antigen / Q000032:analysis; D004317:Doxorubicin / Q000008:administration & dosage; D004591:Electrophoresis, Polyacrylamide Gel; D005770:Gastrointestinal Neoplasms / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000494:pharmacology; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D004317:Doxorubicin