A Novel Monoclonal Antibody Targeting Cancer-Specific Plectin Has Potent Antitumor Activity in Ovarian Cancer

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Cancer-specific plectin (CSP) is a pro-tumorigenic protein found on the surface of major cancers, including ovarian cancer (OC).
• The therapeutic potential of targeting CSP has not been previously explored despite its accessibility and functional role.

Purpose of the Study:

• To investigate the anticancer effects of a novel monoclonal antibody, 1H11, targeting CSP in ovarian cancer models.
• To evaluate the efficacy of 1H11 as a monotherapy and in combination with chemotherapy.

Main Methods:

• In vitro studies using OC cell lines and in vivo studies using a subcutaneous ovarian cancer model.
• Assessment of 1H11's affinity, specificity, internalization, cytotoxicity, cell cycle arrest, migration inhibition, and effects on ROS and JAK2-STAT3 pathway.
• Evaluation of in vivo tumor growth inhibition, Ki67 expression, tumor necrosis, and chemosensitivity to cisplatin.

Main Results:

• 1H11 demonstrated high affinity and specificity for CSP, with rapid internalization.
• In vitro, 1H11 induced significant cytotoxicity, G0/G1 arrest, and reduced migration, linked to increased ROS and decreased JAK2-STAT3 activation.
• In vivo, 1H11 inhibited tumor growth by 65%, induced 30% necrosis, and enhanced cisplatin efficacy by 60%.

Conclusions:

• Targeting CSP with the 1H11 antibody shows significant anticancer activity against ovarian cancer.
• 1H11 exhibits potent monotherapy effects and enhances chemotherapy response, suggesting its potential for clinical development in ovarian cancer treatment.