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Updated: Apr 20, 2026
Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
Immunotherapy targeting folate receptor induces cell death associated with autophagy in ovarian cancer
Yunfei Wen1, Whitney S Graybill2, Rebecca A Previs1
1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Purpose:
Cancer cells are highly dependent on folate metabolism, making them susceptible to drugs that inhibit folate receptor activities. Targeting overexpressed folate receptor alpha (FRα) in cancer cells offers a therapeutic opportunity. We investigated the functional mechanisms of MORAB-003 (farletuzumab), a humanized mAb against FRα, in ovarian cancer models.
Experimental Design:
We first examined FRα expression in an array of human ovarian cancer cell lines and then assessed the in vivo effect of MORAB-003 on tumor growth and progression in several orthotopic mouse models of ovarian cancer derived from these cell lines. Molecular mechanisms of tumor cell death induced by MORAB-003 were investigated by cDNA and protein expression profiling analysis. Mechanistic studies were performed to determine the role of autophagy in MORAB-003-induced cell death.
Results:
MORAB-003 significantly decreased tumor growth in the high-FRα IGROV1 and SKOV3ip1 models but not in the low-FRα A2780 model. MORAB-003 reduced proliferation, but had no significant effect on apoptosis. Protein expression and cDNA microarray analyses showed that MORAB-003 regulated an array of autophagy-related genes. It also significantly increased expression of LC3 isoform II and enriched autophagic vacuolization. Blocking autophagy with hydroxychloroquine or bafilomycin A1 reversed the growth inhibition induced by MORAB-003. In addition, alteration of FOLR1 gene copy number significantly correlated with shorter disease-free survival in patients with ovarian serous cancer.
Conclusions:
MORAB-003 displays prominent antitumor activity in ovarian cancer models expressing FRα at high levels. Blockade of folate receptor by MORAB-003 induced sustained autophagy and suppressed cell proliferation.
Insights
MORAB-003 (farletuzumab) effectively reduced ovarian cancer growth by inducing autophagy in high folate receptor alpha (FRα)-expressing tumors. This targeted therapy suppressed cancer cell proliferation, offering a promising strategy for FRα-positive ovarian cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Cancer cells exhibit a high dependency on folate metabolism.
- Folate receptor alpha (FRα) is overexpressed in various cancer cells, presenting a therapeutic target.
- Targeting FRα offers a potential strategy for cancer treatment.
Purpose of the Study:
- To investigate the functional mechanisms of MORAB-003 (farletuzumab), a monoclonal antibody targeting FRα.
- To evaluate the efficacy of MORAB-003 in ovarian cancer models.
- To elucidate the molecular pathways, including autophagy, involved in MORAB-003's anti-cancer effects.
Main Methods:
- Assessed FRα expression in human ovarian cancer cell lines.
- Evaluated MORAB-003's effect on tumor growth in orthotopic mouse models.
- Utilized cDNA and protein expression profiling to analyze molecular mechanisms.
- Investigated the role of autophagy in MORAB-003-induced cell death.
Main Results:
- MORAB-003 significantly inhibited tumor growth in ovarian cancer models with high FRα expression.
- MORAB-003 reduced cancer cell proliferation but did not significantly induce apoptosis.
- MORAB-003 modulated autophagy-related genes, increasing LC3-II expression and autophagic vacuolization.
- Blocking autophagy reversed the growth-inhibitory effects of MORAB-003.
- Alterations in FOLR1 gene copy number correlated with reduced disease-free survival in ovarian cancer patients.
Conclusions:
- MORAB-003 demonstrates significant antitumor activity in FRα-expressing ovarian cancers.
- MORAB-003 induces sustained autophagy and suppresses proliferation in ovarian cancer cells.
- Targeting FRα with MORAB-003 represents a viable therapeutic approach for specific ovarian cancer subtypes.
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