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

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.