Internalization with high targeting potential of mouse monoclonal antibody ONS-M21 recognizing human malignant glioma antigen.
In order to evaluate the targeting potential of mouse monoclonal antibody ONS-M21 recognizing a human astrocytoma- and medulloblastoma-associated antigen, the internalization ability of this antibody and the selective cytotoxicity in the toxin-conjugated form were examined. Internalization assay with 125I-labeled ONS-M21 showed that about 20% of the total radioactivities was detected in the cellular fraction of human medulloblastoma cell line ONS-76 cells and that the reaction reached a plateau level in 30 min. To examine the selective delivery capacity of a high molecular substance in place of 125I, an immunotoxin was prepared with ricin A chain and ONS-M21 via disulfide bonds. A cytotoxic effect against ONS-76 cells was found with [3H]thymidine incorporation assay using the immunotoxin, but not against antigen-negative HuH-7 and SW480 cells. These results suggest that ONS-M21 could effectively deliver toxins, chemotherapeutic agents or radionuclei to malignant glioma specifically.
Shimizu
K
K
Department of Neurosurgery, Osaka University Medical School, Suita City, Japan.
Park
K C
KC
Tamura
K
K
Kishima
H
H
Kawata
H
H
Yoshimura
Y
Y
Sekimori
Y
Y
Miyao
Y
Y
Hayakawa
T
T
D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis*; D001254:Astrocytoma / Q000276:immunology; D002470:Cell Survival; D005069:Evaluation Studies as Topic; D005910:Glioma / Q000276:immunology*; D006801:Humans; D000922:Immunotoxins; D008527:Medulloblastoma / Q000276:immunology; D051379:Mice; D012276:Ricin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000922:Immunotoxins; D012276:Ricin