Cytotoxicity of ^Sup 111^In-Labeled Antibodies

In the June issue of Molecular Cancer Therapy (2005;4:927-937), Michel et al. from the Center for Molecular Medicine and Immunology (Belleville, NJ) reported on a study designed to assess the in vitro cytotoxicity of anti-HER-2 antibodies conjugated to ^sup 111^In or ^sup 125^I. Target cells in the study were the breast carcinoma SK- BR-3 and the ovarian carcinoma SK-OV-3.ipl. Antibody accumulation and catabolism during a 2-3-day incubation with antibody were measured to assure that uptake was sufficient to make cell killing feasible. Cells were incubated for 2 days with the labeled antibody, then assayed for colony-forming units with a limiting dilution assay to test for cytotoxicity. SK-BR-3 cells were strongly killed, and SK- OV-3.ip.l cells were more resistant to killing. However, a 2- antibody mixture produced 100% killing in the breast carcinoma cells and somewhat enhanced killing in the ovarian carcinoma cells. ‘”In- labeled antibodies to other high-density antigens, epithelial glycoprotein-1, and epithelial glycoprotein-2, also killed these target cells. Unlabeled antibodies produced much less cytotoxicity, and, although ^sup 131^I-labeled antibodies resulted in high levels of nonspecific cytotoxicity, they produced essentially no specific cytotoxicity.

Molecular Cancer Therapy Copyright Society of Nuclear Medicine Aug 2005