Development and Novel Uses of Antibodies in Epithelial Ovarian Cancer

Abstract

Abstract : We studied the therapeutic value of Sindbis vectors for advanced metastatic ovarian cancer by using two mouse models; a SCID xenograft model growing human ES-2 ovarian cancer cells, and a syngeneic C57BL/6 model growing mouse MOSEC ovarian cancer cells. Imaging, histological, and molecular data demonstrated that Sindbis vectors systemically and specifically kill metastasized tumors in the peritoneal cavity, leading to significant suppression of the carcinomatosis in both animal models. Utilization of different bioluminescent markers for imaging studies demonstrated an excellent correlation between vector and tumor localization in vivo. Sindbis vector suppression of murine MOSEC tumor cells indicate that Sindbis tumor specificity is not attributable to a species difference between human tumor and mouse normal cells. Sindbis virus infects mammalian cells using the 67-kDa laminin receptor (LAMR). Immunohistochemical staining indicates that LAMR is elevated in tumor vs. normal cells. Down-regulated expression of LAMR with siRNA significantly reduces the infectivity of Sindbis vectors. Thus, tumor overexpression of the LAMR may explain the specificity and efficacy that Sindbis vectors. Incorporation of cytokine genes such as interleukin-12 and interleukin-15 genes enhances the vector's efficacy. Sindbis viral vectors may be promising agents for both specific detection and suppression of metastatic ovarian cancer.