STEM CELL- AND DENDRITIC CELL-BASED CANCER IMMUNOTHERAPY TARGETING CANCER STEM CELLS

Abstract

IN THIS PHD PROJECT, WE EXPLORED THE POTENTIAL OF STEM CELL- AND DENDRITIC CELL-BASED CANCER IMMUNOTHERAPY TO TARGET CANCER METASTASIS AND CANCER STEM CELL (CSC). IN STEM CELL PART, WE GENERATED NSCS FROM HIPSCS. WE FOUND THAT NEURONAL NITRIC OXIDE SYNTHASE (NNOS) WAS A RELEVANT REGULATOR IN CONTROLLING HIPSC-NSCS TUMOR TROPISM, AND NNOS INHIBITION COULD SENSITIZE POORLY MIGRATORY NSCS, HENCE IMPROVING THEIR TUMOR TROPISM. FURTHERMORE, OUR RESULTS DEMONSTRATE THE TREATMENT UTILIZING HIPSC-NSCS ENGINEERED WITH CD40 LIGAND (CD40L) COULD SIGNIFICANTLY IMPEDE THE TUMOR GROWTH. IN DENDRITIC CELL PART, WE CONFER CERTAIN CANCER STEM-LIKE PROPERTIES TO HUMAN GLIOMA CELLS BY REPROGRAMMING. HUMAN DENDRITIC CELLS LOADED WITH LYSATES OF CANCER STEM-LIKE CELLS WERE CAPABLE OF ELICITING CSC ANTIGEN SPECIFIC T-CELL RESPONSE IN VITRO. THEREFORE, WE ENVISION THAT REPROGRAMMED CANCER STEM-LIKE CELLS CAN BE USED AS A READILY ACCESSIBLE SOURCE TO PROVIDE CSC-RELATED ANTIGENS FOR DENDRITIC CELL IMMUNOTHE