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.