Fig. 1: Schematic showing the mouse experimental design and procedure for optogenetic perioperative immunotherapy mediated by FLICs-loaded hydrogel implants.
From: Optogenetic-controlled immunotherapeutic designer cells for post-surgical cancer immunotherapy
Far-red light-controlled immunomodulatory engineered cells (FLICs) were encapsulated within a polysaccharide-based biocompatible hydrogel that allows free diffusion of oxygen, ions, and secreted proteins while simultaneously shielding the encapsulated cells from the host immune system. After surgical resection of the B16F10 melanoma tumors in mice, the encapsulated FILCs were implanted subcutaneously at the surgical wound site. An engineered FRL-activated cyclic diguanylate monophosphate (c-di-GMP) synthase (BphS) from a bacterium converts intracellular guanylate triphosphate (GTP) into cyclic diguanylate monophosphate (c-di-GMP), which binds to the hybrid transactivator p65-VP64-BldD, thereby facilitating its translocation into the nucleus, where the transactivator binds its chimeric promoter PFRL to induce transcription of genes for mouse immunomodulatory cytokines (IFN-β, TNF-α, and IL-12). These cytokines promote activation of innate immunity, including antitumor NK cell and T cell responses to prevent tumor relapse.
