Therapeutics: Glypican 3 (GPC3)
In vitro and mouse studies suggest a GPC3-targeting immunotoxin could help treat liver cancer. The immunotoxin consisted of a peptide fragment of a Pseudomonas exotoxin fused to an anti-GPC antibody that inhibited oncogenic WNT signaling. In human liver cancer cell lines, the immunotoxin decreased proliferation compared with a fusion protein containing the exotoxin and an anti-GPC antibody that did not inhibit WNT signaling. In mice with xenograft liver tumors, IV immunotoxin decreased tumor growth and increased survival compared with the control fusion protein. Also in the model, the immunotoxin and the generic chemotherapeutic irinotecan synergistically decreased tumor growth compared with either agent alone. Next steps include additional preclinical evaluation of the immunotoxin before clinical testing.
Chugai Pharmaceutical Co. Ltd. and Roche have GC33 (RG7686; RO5137382), an anti-GPC3 antibody, in Phase II testing to treat liver cancer. ...