Project description:In this study we are examining the paracrine effect induced by feline calicivirus (FCV) infection on stress granule (SG) accumulation. We provided an understanding of paracrine granules function and specificity through their affinity purification followed RNAseq to systematically analyse their RNA content.
Project description:Cellular immunotherapies show remarkable efficacy against hematological malignancies; but face challenges against solid tumors largely attributed to the lack of tumor-specific antigens and immunosuppressive tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), expressing fibroblast activation protein (FAP) are key contributors in shaping this immunosuppressive landscape, yet effective targeting strategies remain an ongoing challenge. Here, we describe MiNK-215, a novel allogeneic human invariant natural killer T (iNKT) cell therapy, engineered to express a FAP-targeting chimeric antigen receptor (CAR) and secrete interleukin-15 (IL-15) to remodel the TME and enhance anti-tumor activity. MiNK-215 modulated multifunctional immune responses by enhancing T cell responsiveness, dendritic cell activation, M1 macrophage polarization, and tumor killing. In a lung tumor mouse model, MiNK-215 depleted FAP+ CAFs, enhanced antigen-specific T cell infiltration, and promoted durable anti-tumor immunity without off-target toxicity. These findings extended to human organoid models of treatment-refractory Microsatellite Stable Colorectal Cancer (MSS-CRC) liver metastases, establishing FAP-CAR iNKT cells as a promising strategy to overcome immunotherapy resistance in solid tumors.
Project description:Astrocytes express a vitamin B12 uptake receptor, CD320/TCblR, that is regulated by S1P1 signaling. In search of genes controlled under B12 deficiency in astrocytes, we employed RNA-seq using RNA of astrocytes cultured in normal or B12 deficient media.