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 wit...

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Bibliographic Details
Published in:Cancer letters 1998-05, Vol.127 (1), p.171-176
Main Authors: Shimizu, Keiji, Park, Kae Chang, Tamura, Kazuyoshi, Kishima, Haruhiko, Kawata, Hiromitsu, Yoshimura, Yasushi, Sekimori, Yasuo, Miyao, Yasuyoshi, Hayakawa, Toru
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal
Antigens, Neoplasm - analysis
Astrocytoma - immunology
Biological and medical sciences
Cell Survival
Evaluation Studies as Topic
Glioma - immunology
Humans
Immunotoxin
Immunotoxins
Internalization
Malignant glioma
Medical sciences
Medulloblastoma - immunology
Mice
Monoclonal antibody
Neurology
Ricin - pharmacology
Ricin A
Tumor Cells, Cultured
Tumors of the nervous system. Phacomatoses
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Summary: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.
ISSN:0304-3835
1872-7980
DOI:10.1016/S0304-3835(98)00030-5