A monoclonal antibody W1 blocks mesothelin-mediated tumor progression
Year: 2025
Type: article
Abstract: Mesothelin (MSLN) represents an attractive and potential biomarker for targeted cancer therapy. Although MSLN has been implicated in mediating tumorigenesis, its precise physiological function remains incompletely elucidated. Moreover, only a limited number of antibodies have been reported to directly inhibit its function in tumor progression. In this study, we confirmed that the N-terminal domain 1 (D1) of MSLN serves as the key region responsible for mediating binding to tumor cells and promoting migration and invasion through the activation of the matrix metalloproteinase-7 (MMP7) pathway. We further identified two monoclonal antibodies, W1 and A12H, which specifically bind to D1 and domain 3 (D3) of MSLN, respectively. W1 effectively inhibits the interaction between D1 and tumor cells, thereby suppressing cell migration and invasion via interference with MSLN-mediated signaling pathways. In contrast, A12H, which targets D3, does not exhibit a similar functional blockade. Additionally, W1 significantly reduces the tumor burden in mice bearing MSLN-positive tumor cells. Together, these findings provide mechanistic insights into the role of D1 in driving tumor progression and reinforce the potential of MSLN as a therapeutic biomarker. The antibody W1 emerges as a promising candidate, offering novel perspectives for developing immunotherapeutic strategies against MSLN-related cancers.
Source: Molecular Therapy Oncology
Authors: Qingguang Wang, Guangcan Cao, Mingxin Li, Rui Gong
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,900
OpenAlex ID: W4416420456