Codrituzumab is a humanized monoclonal antibody targeted at glypican-3 (GPC3), which is a member of the glypican family. This drug is developed by Chugai Pharmaceutical in combination with Roche and has been investigated in the treatment of liver cancer. The specific expression of GPC3 is high in hepatocellular carcinoma (HCC) tissues, which suggests that GPC3 has obvious sensitivity and specificity in the diagnosis of hepatocellular carcinoma, and can be used as a new target for the treatment of hepatocellular carcinoma. Codrituzumab did not show significant inhibition of GPC3 in the phase I trial in combined with sorafenib and the phase II trial placebo-controlled study in patients with advanced liver cancer. Codrituzumab did not show significant inhibition of GPC3 in phase I trials and phase II trials combined with sorafenib in patients with advanced liver cancer. However, the effect of codrituzumab in the treatment of liver cancer is still under study. In 2018, researchers conducted trials such as the distribution of codrituzumab and the impact of overall survival in patients with hepatocellular carcinoma. In the combined analysis of tumor cell surface antigen GPC3 and NK cell surface antigen CD16 in patients with liver cancer, it was found that codrituzumab only had a certain therapeutic effect on patients with high expression level of GPC3 and CD16. These results suggest that GPC3 and CD16 can be used as a composite biomarker to select hepatocellular carcinoma patients for codrituzuma.
Glypican-3 (GPC3), the target molecule of codrituzumab, is a member of the proteoglycan family found in the study of simpson-golabi-behmelsyndrome (SGBS). GPC3 plays an important role in regulating cell growth and differentiation, and is closely related to the occurrence and development of hepatocellular carcinoma. The results showed that GPC3 was highly expressed in hepatocellular carcinoma, but not expressed or at a low level in adult normal tissues, suggesting that GPC3 has obvious sensitivity and specificity in the diagnosis of hepatocellular carcinoma. GPC3 can be used as a new tumor biomarker and a therapeutic target for hepatocellular carcinoma. At the cellular level, GPC3 can regulate a variety of growth factor signaling pathways, including Wnts, hedgehogs, and ERK, to promote the growth of hepatoma cells. The mechanism of monoclonal antibody codrituzumab in the treatment of hepatocellular carcinoma may through the interaction with CD16/Fc γ RIIIa when binding to GPC3 expressed on the tumor cells, to trigger antibody-dependent cytotoxicity and kill tumor cells.
Fig.1 Mechanism of Action of Codrituzumab
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