Abstract 2817: DCVex(TM): A novel DC-targeted vector platform for cancer immunotherapy

Abstract

Abstract Dendritic cells (DCs) are essential for the initiation of T cell responses and are therefore an attractive target for cancer immunotherapy. The DC vaccine, Provenge®, as well as a number of on-going clinical trials, have in principle validated this concept. However, the currently pursued strategy of ex vivo immunization of DCs is time-consuming and costly. We have developed a 3rd generation, integration-deficient lentivector platform, DCVex(TM), which is designed to deliver tumor antigen-encoding genes directly to DCs in vivo by targeting the DC-SIGN receptor. Mice immunized with DCVex(TM) vectors expressing a variety of model antigens developed strong, dose-dependent poly-functional and cytotoxic antigen-specific CD8 T cell responses, as assessed by intracellular cytokine staining and in vitro cytotoxic T lymphocyte assays. Repeated immunizations resulted in boosting of the T cell responses, indicating the absence of induction of inhibitory anti-vector immunity. Importantly, in stringent therapeutic tumor models (e.g., B16F10 footpad melanoma and CT26 lung metastasis models), immunization with tumor antigen-encoding vectors protected the majority of animals from death in a dose-dependent manner. These findings demonstrate the potential of DCVex(TM) as a novel cancer vaccine platform suitable for in vivo DC immunization. Citation Format: Tina C. Albershardt, Semih U. Tareen, Jared M. Odegard, David J. Campbell, Patrick Flynn, Scott H. Robbins, Peter Berglund, Jan H. ter Meulen. DCVex(TM): A novel DC-targeted vector platform for cancer immunotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2817. doi:10.1158/1538-7445.AM2014-2817