• HOME

3-1. Proteomics Study on Cell-surface Proteins of Cancers Identifies a New Cancer Antigen GPC1 for Therapeutic Antibody

Through a quantitative proteomics approach named iTRAQ, we searched for new cancer antigens on esophageal squamous cell carcinoma (ESCC) cell lines and found that Glypican-1 (GPC1) is highly expressed in many ESCC cells. GPC1 expression is high in primary lesions and lymph node metastases of ESCC patients, but not in normal tissues. Moreover, among patients with ESCC, those with GPC1 high tumors exhibited poor survival compared to those with GPC1 low tumors (Hara et al., Br J Cancer, 2016). GPC1 is a member of a family of heparin sulphate proteoglycans (HSPGs) and is a co-receptor for heparin-binding growth factors such as HB-EGF, HGF and FGF-2. GPC1 blocking by anti-GPC1 antibody in mice xenografted with ESCC successfully inhibited tumor growth in both ADCC/CDC-dependent and ?independent manners (Harada et al., Oncotarget, 2017). Furthermore, cancer-specific drug delivery by anti-GPC1 antibody-drug conjugate (GPC1-ADC) showed a powerful anti-tumor effect on a mouse model of uterine cervical cancer(Matsuzaki et al., Int J Cancer, 2017) . Pre-clinical evaluation of GPC-ADC is on the way to develop this agent as a new aiticancer agent on intractable cancers in humans.