Open AccessA Monoclonal Antibody, KM10 Reactive with Human Gastrointestinal Cancer and Its Application for Immunotherapy
Author(s) -
Ohyanagi Harumasa,
Ishida Hidefumi,
Ishida Tsuneyuki,
Soyama Nobuhiko,
Yamamoto Masahiro,
Okumura Shuichi,
Kano Yoshiaki,
Ueda Yasuo,
Saitoh Yoichi
Publication year - 1988
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1988.tb01566.x
Subject(s) - immunoconjugate , monoclonal antibody , antibody , cancer , immunoperoxidase , pathology , immunotherapy , antigen , spleen , biology , in vivo , cancer research , microbiology and biotechnology , medicine , immunology
A monoclonal antibody, KM10 (IgG 1 ) 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 125 I‐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 antitnmor activity was observed in vivo with KM10‐ADM conjugate, while this conjugate was less toxic than free ADM.