Liver Cancer Regression by an Immunotoxin Targeting Glypican-3 Through Inhibiting Wnt Signaling and Protein Synthesis

摘要

Glypican-3 is a cell surface glycoprotein that associates with Wnt in liver cancer. We develop two antibodies targeting Glypican-3, HN3 and YP7. The first antibody recognizes a functional epitope and inhibits Wnt signaling, whereas the second antibody recognizes a C-terminal epitope but does not inhibit Wnt signaling. Both are fused to a fragment of Pseudomonas exotoxin A (PE38) to create immunotoxins. Interestingly, the immunotoxin based on HN3 (HN3-PE38) has superior anti-tumor activity as compared to YP7 (YP7-PE38) both in vitro and in vivo.