Abstract
656
A novel oncofetal antigen Glypican-3 (GPC-3) has been reported to be highly expressed in primary hepatocellular carcinoma (HCC) and melanoma. Our data using a commercial anti-GPC-3 mAb confirmed a strong signal in 70% of HCC tumors tested by immunohistochemistry. Expression profiling of 32 normal human tissues showed that expression of GPC-3 was restricted to placenta and faint cytoplasmic staining in normal kidney. We also evaluated breast, lung, uterus and ovarian cancer tissue microarrays for GPC-3 expression. Thirty-two out of 42 ovarian tumors (76%) showed elevated GPC-3 expression. We found moderate to high levels of expression of GPC-3 in HCC, colon cancer and melanoma cell lines and undetectable levels in normal renal cells by quantitative FACS. Using an anti-GPC-3 mAb conjugated to the potent cytotoxic agent monomethylauristatin F, we showed specific growth inhibition of GPC-3+ cells in vitro, thus indicating internalization of the antibody-target complex. With the restricted normal tissue expression of GPC-3 and efficient internalization of the antibody-drug conjugate (ADC), an anti-GPC-3 ADC may be useful for targeted therapy of hepatocellular carcinomas. Possible additional indications are in ovarian cancer and melanomas.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA