Actionable spontaneous antibody responses antagonize malignant progression in ovarian carcinoma
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This study identified spontaneous antibody responses targeting SDCBP in ovarian carcinoma and endometriosis, and demonstrated that antibodies against SDCBP reduced tumor growth in mouse models.
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Abstract
OBJECTIVE: To demonstrate that shared antibody responses in endometriosis and endometriosis-associated ovarian cancer spontaneously antagonize malignant progression and can be leveraged to develop future immunotherapies.
METHODS: B cells from cyopreserved clear cell ovarian carcinoma (CCC, n = 2), endometrioid ovarian carcinoma (EC, n = 2), and endometriomas (n = 2) were isolated, activated, and EBV-immortalized. Antibodies were purified from B cell supernatants and used for screening arrays containing most of the human proteome. Targets were prioritized based on accessibility (transmembrane or secreted proteins), expression in endometriosis and cancer, and concurrent IgA and IgG responses. We focused on antibodies targeting tumor-promoting syndecan binding protein (SDCBP) to demonstrate anti-tumor activity. Immunoblots and qPCR were performed to assess SDCBP expression in ovarian cancer and endometriosis cell lines and tumor samples. Recombinant IgG4 was generated using the variable heavy and light chains of dominant B cell receptors (BCRs) reacting against the extracellular domain of SDCBP, and used in in vivo studies in human CCC- and high-grade serous ovarian carcinoma (HGSOC)-bearing immunodeficient mice.
RESULTS: Nine accessible proteins detected by both IgA and IgG were identified in all samples - including SDCBP, which is expressed in ovarian carcinomas of multiple histologies. Administration of α-SDCBP IgG4 in OVCAR3 (HGSOC), TOV21G and RMG-I (CCC) tumor-bearing mice significantly decreased tumor volume compared to control irrelevant IgG4.
CONCLUSIONS: Spontaneous antibody responses exert suboptimal but measurable immune pressure against malignant progression in ovarian carcinomas. Using tumor-derived antibodies for developing novel immunotherapeutics warrants further investigation.
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Too few in-corpus citations on either side for a chart; here are the lists.
Cites (4)
- <i>ARID1A</i> Mutations in Endometriosis-Associated Ovarian Carcinomas 2010
- Identification of an Invasive, N-Cadherin-Expressing Epithelial Cell Type in Endometriosis Using a New Cell Culture Model 2001
- Multifocal endometriotic lesions associated with cancer are clonal and carry a high mutation burden 2015
- Risk of Gynecologic Cancer According to the Type of Endometriosis 2018
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Source provenance
- europepmc
- last seen: 2026-06-04T01:30:01.192114+00:00
- openalex
- last seen: 2026-06-10T17:14:06.276822+00:00
- pubmed
- last seen: 2026-06-11T06:18:46.262221+00:00
License: CC0
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