Engineered DNA Vaccination against Follicle-Stimulating Hormone Receptor Delays Ovarian Cancer Progression in Animal Models.

Affiliation

Vaccine and Immunotherapy Center, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA 19104, USA. Electronic address: [Email]

Abstract

Ovarian cancer presents in 80% of patients as a metastatic disease, which confers it with dismal prognosis despite surgery and chemotherapy. However, it is an immunogenic disease, and the presence of intratumoral T cells is a major prognostic factor for survival. We used a synthetic consensus (SynCon) approach to generate a novel DNA vaccine that breaks immune tolerance to follicle-stimulating hormone receptor (FSHR), present in 50% of ovarian cancers but confined to the ovary in healthy tissues. SynCon FSHR DNA vaccine generated robust CD8+ and CD4+ cellular immune responses and FSHR-redirected antibodies. The SynCon FSHR DNA vaccine delayed the progression of a highly aggressive ovarian cancer model with peritoneal carcinomatosis in immunocompetent mice, and it increased the infiltration of anti-tumor CD8+ T cells in the tumor microenvironment. Anti-tumor activity of this FSHR vaccine was confirmed in a syngeneic murine FSHR-expressing prostate cancer model. Furthermore, adoptive transfer of vaccine-primed CD8+ T cells after ex vivo expansion delayed ovarian cancer progression. In conclusion, the SynCon FSHR vaccine was able to break immune tolerance and elicit an effective anti-tumor response associated with an increase in tumor-infiltrating T cells. FSHR DNA vaccination could help current ovarian cancer therapy after first-line treatment of FSHR+ tumors to prevent tumor recurrence.

Keywords

DNA vaccine,cancer vaccine,follicle-stimulating hormone receptor,immunotherapy,ovarian cancer,

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