Data from IMGN853 Induces Autophagic Cell Death in Combination Therapy for Ovarian Cancer

• DOI: 10.1158/2767-9764.c.7742997
• Publication Date: 2025-03-28T15:28:27Z
• Authors: Anca Chelariu-Raicu; Thanh Chung Vu; Sujanitha Umamahe...; Elaine Stur; Pahul Hanjra; Yunah Han; Min Hu; Jerome Lin; Barrett C. Lawson; Jinsong Liu; Anil K. Sood; Yunfei Wen
• Keywords: Cancer Therapy

<div>Abstract<p>Antibodies targeting folate receptor 1 (FOLR1) induce autophagic cell death in addition to antibody-dependent cytotoxicity, but the biological relevance of anti-FOLR1 antibody–induced autophagy for clinical applications remains unclear. In this study, we investigated role triggered by IMGN853 (mirvetuximab soravtansine), an FOLR1-targeted antibody–drug conjugate, and explored potential combinations with chemotherapeutic drugs used ovarian cancer treatment. We discovered that FOLR1 was predominantly expressed epithelial cells, similar expression levels observed both primary tumors metastatic omental from patients high-grade serous (HGSC). Treatment improved survival mice bearing patient-derived xenografts HGSC, enhanced flux, induced HGSC cells. Additionally, it increased autophagy-related marker LC3B-II as marked cleaved caspase-3, a manner dependent on beclin-1, models. Notably, topotecan or anti–VEGF-A antibody (B20) significantly reduced tumor growth compared alone, whereas no significant effect olaparib. Our findings indicate induces death, which contributes its tumor-inhibiting effects. The identification these effective combination therapies mechanisms behind FOLR1-mediated could facilitate further development IMGN853.</p>Significance:<p>FOLR1 is heterogeneously overexpressed cancer. examined combined effects conjugate (IMGN853) other drugs, including topotecan, antibody, These contribute continued treatment cancer.</p></div>