Abstract 1652: Optogenetic immunoengineering to develop improved anti-cancer immunotherapy

Abstract The application of current channelrhodopsin-based optogenetic tools is limited by the lack of strict ion selectivity and the inability to extend the spectra sensitivity into the near-infrared (NIR) tissue transmissible range. Here we present an NIR-stimulable optogenetic platform (termed “Opto-CRAC”) that selectively and remotely controls Ca2+ oscillations and Ca2+-responsive gene expression to regulate the function of model cellular systems, as well as cells of the immune system. When coupled to upconversion nanoparticles, the optogenetic operation window is shifted from the visible range to NIR wavelengths to enable wireless and remote photoactivation of Ca2+-dependent signaling and optogenetic modulation of immunoinflammatory responses. In a mouse model of melanoma by using ovalbumin as surrogate tumor antigen, Opto-CRAC has been shown to act as a genetically-encoded “photoactivatable adjuvant” to improve antigen-specific immune responses to specifically destruct tumor cells. In addition, we have extended similar engineering approaches to photomanipulate membrane contact sites that play critical roles in controlling lipid metabolism and calcium signaling in cancer cells. Our study represents a solid step forward towards the goal of improving spatial and temporal control of anti-cancer therapy through optogenetic immunoengineering. Note: This abstract was not presented at the meeting. Citation Format: Lian He, Nhung Nguyen, Gang Han, Yun Huang, Yubin Zhou. Optogenetic immunoengineering to develop improved anti-cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1652. doi:10.1158/1538-7445.AM2017-1652