Abstract 2410: Development of a genetically-optimized whole tumor cell vaccine for ovarian cancer using HSV-derived glycoprotein D

Abstract

Abstract Background: Dendritic cell (DC) vaccines offer a promising addition to standard treatment for ovarian cancer with surgery and chemotherapy. We have previously shown that treatment of whole tumor cells with replication-deficient herpes simplex virus (HSV) results in a potent, specific T-Cell response to ovarian tumors. We sought to improve vaccine efficiency by isolating and comparing two specific components of HSV-treated SK-OV-3-pulsed DCs: glycoprotein D (gD) and IL12p70. Methods: SK-OV-3 cells were treated with HSV1716 or transfected with HSV-1-derived gD engineered to express a similar amount of surface of gD. We further engineered these cells to express IL12p70 by lentiviral transduction. Theses cells were UVB-irradiated and pulsed with DCs. ELISA was used to measure the kinetics of the IL12p70 burst of each tumor-pulsed DC, as well as to compare the naïve, autologous lymphocyte priming responses of each cell line. Results: IL12p70 was increased 3-fold with gD-SKOV3 compared to HSV-SKOV3, while following the same kinetic curve (646 ± 45.2 pg/mL v. 234 ± 24.2 pg/mL; p <0.01). gD-SKOV3 also resulted in a 2-fold higher priming response. Both the IL12p70 burst and priming response were blocked by treatment of SKOV3-gD cells with an antibody to gD. With the addition of IL12 to these cells, SKOV3-gD, but not SKOV3-HSV cells, resulted in significantly higher and more prolonged IL12 burst than that of SKOV3-IL12 cells alone. Conclusions: Our in vitro results suggest a synergistic effect of IL12p70 and gD that is not seen with infection by intact HSV-1. We have isolated two key components from HSV, cytokine stimulation and gD-mediated blockade of immunosuppression, that in combination result in a more potent, specific immune response to ovarian cancer tumor cells. We can now utilize these key components to engineer a more efficient whole tumor cell vaccine for EOC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2410.