期刊
GYNECOLOGIC ONCOLOGY
卷 173, 期 -, 页码 114-121出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2023.03.020
关键词
Tumor immunology; B cell cancer; Immunotherapy; Endometriosis; Ovarian cancer
The study demonstrates that shared antibody responses in endometriosis and endometriosis-associated ovarian cancer can counteract malignant progression and have the potential for developing immunotherapies. Antibodies targeting tumor-promoting syndecan binding protein (SDCBP) show anti-tumor activity in mouse models of ovarian carcinoma. These findings suggest that utilizing tumor-derived antibodies may be a promising approach for future immunotherapies.
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 immu-notherapies.Methods. B cells from cyopreserved clear cell ovarian carcinoma (CCC, n = 2), endometrioid ovarian carci-noma (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 endometri-osis 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 carci-noma (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 alpha-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 immuno-therapeutics warrants further investigation.(c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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