Chimeric Anti-Glypican 1 Antibodies Exert Antitumor Activities in Xenograft Models of Lung and Pancreatic Cancers
Year: 2026
Type: article
Abstract: Glypican-1 (GPC1) has emerged as a critical mediator of malignant tumor progression. GPC1 plays essential roles in regulating various signaling pathways involved in tumor cell proliferation, invasiveness, and tumorigenesis. Overexpression of GPC1 in tumors mediates oncogenic transformation, epithelial-to-mesenchymal transition, metastatic dissemination, and therapeutic resistance. Accordingly, GPC1-targeted therapeutic strategies have been investigated in clinical and preclinical studies. However, clinical efficacy has been limited. We previously developed an anti-GPC1 monoclonal antibody (mAb), G1Mab-28 (mouse IgG1, κ), which exhibits high affinity and specificity for GPC1. In the present study, we generated recombinant isotype-converted G1Mab-28, including G1Mab-28-mG2a (mouse IgG2a) and G1Mab-28-hG1 (human IgG1). Both mAbs recognized GPC1-expressing human tumor cell lines, including lung squamous cell carcinoma PC-10 and pancreatic ductal adenocarcinoma PK-45H, by flow cytometry. Moreover, both mAbs exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against those cell lines. In mouse xenograft models, treatment with the mAbs resulted in potent antitumor efficacy against PC-10 and PK-45H tumors. Collectively, these findings support the therapeutic potential of G1Mab-28 for the treatment of GPC1-positive tumors.
DOI: 10.3390/ijms27104181
Institutions: Tohoku University, Microbial Chemistry Research Foundation
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: G1057214278, Development of an analytical method for virus neutralizing mAbs using surface IgG of hybridoma cells, CasMab法を基盤としたがん特異的抗体の臨床開発, G3041078186, GPC3 CAR発現iPS細胞由来ILC/NK細胞の患者体内生存延長と抗腫瘍エフェクター機能向上を目指したリバーストランスレーショナル研究, G494641229, G530779871, CasMab法を駆使したがん特異的抗体の開発とその作用機序の解明, G8496608524
OpenAlex ID: W7160628425
