A glypican-1-targeted antibody-drug conjugate exhibits potent tumor growth inhibition in glypican-1-positive pancreatic cancer and esophageal squamous cell carcinoma
Neoplasia. 2021 Jul 28;23(9):939-950. doi: 10.1016/j.neo.2021.07.006. Online ahead of print.ABSTRACTAn antibody-drug conjugate (ADC) is a promising therapeutic modality because selective and effective delivery of an anti-cancer drug is achieved by drug-conjugated antibody-targeting cancer antigen. Glypican 1 (GPC1) is highly expressed in malignant tumors, including pancreatic ductal adenocarcinoma (PDAC) and esophageal squamous cell carcinoma (ESCC). Herein, we describe the usefulness of GPC1-targeting ADC. Humanized anti-GPC1 antibody (clone T2) was developed and conjugated with monomethyl auristatin E (MMAE) via maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-vc-PABC) linkers (humanized GPC1-ADC[MMAE]). Humanized GPC1-ADC(MMAE) inhibited the growth of GPC1-positive PDAC and ESCC cell lines via inducing cycle arrest in the G2/M phase and apoptosis in vitro. The binding activity of humanized GPC1-ADC(MMAE) with GPC1 was comparable with that of the unconjugated anti-GPC1 antibody. The humanized GPC1-ADC(MMAE) was effective in GPC1-positive BxPC-3 subcutaneously xenografted mice but not in GPC1-negative BxPC-3-GPC1-KO xenografted mice. To assess the bystander killing activity of the humanized GPC1-ADC(MMAE), a mixture of GPC1-positive BxPC-3 and GPC1-negative BxPC-3-GPC1-KO-Luc cells were subcutaneously inoculated, and a heterogenous GPC1-expressing tumor model was developed. The humanized GPC1-ADC(MMAE) inhibited the tumor growth and decreased the luciferase si...
Source: Neoplasia - Category: Cancer & Oncology Authors: Eri Munekage Satoshi Serada Shigehiro Tsujii Keiichiro Yokota Keita Kiuchi Kenji Tominaga Minoru Fujimoto Mizuki Kanda Sunao Uemura Tsutomu Namikawa Taisei Nomura Ichiro Murakami Kazuhiro Hanazaki Tetsuji Naka Source Type: research
More News: Adenocarcinoma | Cancer | Cancer & Oncology | Carcinoma | Esophagus Cancer | Hepatocellular Carcinoma | Liver | Liver Cancer | Pancreas | Pancreatic Cancer | Skin Cancer | Squamous Cell Carcinoma | Urology & Nephrology