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Actionable spontaneous antibody responses antagonize malignant progression in ovarian carcinoma.

Publication ,  Journal Article
Handley, KF; Mehta, S; Martin, AL; Biswas, S; Maharaj, K; Nagy, MZ; Mine, JA; Cortina, C; Yu, X; Sprenger, K; Mandal, G; Innamarato, P ...
Published in: Gynecol Oncol
June 2023

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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Published In

Gynecol Oncol

DOI

EISSN

1095-6859

Publication Date

June 2023

Volume

173

Start / End Page

114 / 121

Location

United States

Related Subject Headings

  • Syntenins
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Mice
  • Immunoglobulin A
  • Humans
  • Female
  • Endometriosis
  • Cell Line, Tumor
  • Carcinoma, Ovarian Epithelial
 

Citation

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Handley, K. F., Mehta, S., Martin, A. L., Biswas, S., Maharaj, K., Nagy, M. Z., … Conejo-Garcia, J. R. (2023). Actionable spontaneous antibody responses antagonize malignant progression in ovarian carcinoma. Gynecol Oncol, 173, 114–121. https://doi.org/10.1016/j.ygyno.2023.03.020
Handley, Katelyn F., Sumit Mehta, Alexandra L. Martin, Subir Biswas, Kamira Maharaj, Mate Z. Nagy, Jessica A. Mine, et al. “Actionable spontaneous antibody responses antagonize malignant progression in ovarian carcinoma.Gynecol Oncol 173 (June 2023): 114–21. https://doi.org/10.1016/j.ygyno.2023.03.020.
Handley KF, Mehta S, Martin AL, Biswas S, Maharaj K, Nagy MZ, et al. Actionable spontaneous antibody responses antagonize malignant progression in ovarian carcinoma. Gynecol Oncol. 2023 Jun;173:114–21.
Handley, Katelyn F., et al. “Actionable spontaneous antibody responses antagonize malignant progression in ovarian carcinoma.Gynecol Oncol, vol. 173, June 2023, pp. 114–21. Pubmed, doi:10.1016/j.ygyno.2023.03.020.
Handley KF, Mehta S, Martin AL, Biswas S, Maharaj K, Nagy MZ, Mine JA, Cortina C, Yu X, Sprenger K, Mandal G, Innamarato P, Powers JJ, Harro CM, Chaurio RA, Anadon CM, Shahzad MM, Flores I, Conejo-Garcia JR. Actionable spontaneous antibody responses antagonize malignant progression in ovarian carcinoma. Gynecol Oncol. 2023 Jun;173:114–121.

Published In

Gynecol Oncol

DOI

EISSN

1095-6859

Publication Date

June 2023

Volume

173

Start / End Page

114 / 121

Location

United States

Related Subject Headings

  • Syntenins
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Mice
  • Immunoglobulin A
  • Humans
  • Female
  • Endometriosis
  • Cell Line, Tumor
  • Carcinoma, Ovarian Epithelial