A monoclonal antibody W1 blocks mesothelin-mediated tumor progression

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Mesothelin (MSLN) is a potential biomarker for targeted cancer therapy.
• The precise physiological function of MSLN in tumorigenesis is not fully understood.
• Limited antibodies are known to inhibit MSLN function in tumor progression.

Purpose of the Study:

• To elucidate the role of MSLN domains in tumor cell binding and progression.
• To identify and characterize novel antibodies targeting MSLN.
• To evaluate the therapeutic potential of MSLN-targeting antibodies.

Main Methods:

• Confirmation of MSLN N-terminal domain 1 (D1) as the key binding region.
• Identification of monoclonal antibodies W1 (targeting D1) and A12H (targeting D3).
• In vitro assays for cell migration and invasion; in vivo tumor burden studies in mice.

Main Results:

• MSLN D1 mediates tumor cell binding, migration, and invasion via the MMP7 pathway.
• Antibody W1 inhibits D1-tumor cell interaction, suppressing migration and invasion.
• Antibody W1 reduces tumor burden in mice; A12H shows no functional blockade.
• W1 demonstrates significant reduction in tumor burden in vivo.

Conclusions:

• MSLN D1 is crucial for driving tumor progression.
• Antibody W1 effectively blocks MSLN-mediated tumor cell functions and reduces tumor growth.
• W1 is a promising candidate for immunotherapeutic strategies against MSLN-related cancers.