title: Antigenically Modified Human Pluripotent Stem Cells Generate Antigen-Presenting Dendritic Cells.
abstract: Human pluripotent stem cells (hPSCs) provide a promising platform to produce dendritic cell (DC) vaccine. To streamline the production process, we investigated a unique antigen-loading strategy that suits this novel platform. Specifically, we stably modified hPSCs using tumour antigen genes in the form of a full-length tumour antigen gene or an artificial tumour antigen epitope-coding minigene. Such antigenically modified hPSCs were able to differentiate into tumour antigen-presenting DCs. Without conventional antigen-loading, DCs derived from the minigene-modified hPSCs were ready to prime a tumour antigen-specific T cell response and further expand these specific T cells in restimulation processes. These expanded tumour antigen-specific T cells were potent effectors with central memory or effector memory phenotype. Thus, we demonstrated that immunocompetent tumour antigen-loaded DCs can be directly generated from antigenically modified hPSCs. Using such strategy, we can completely eliminate the conventional antigen-loading step and significantly simplify the production of DC vaccine from hPSCs.
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore.
authors.forename: Jieming
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Wu
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore.|Department of Biological Sciences, National University of Singapore, Singapore.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000939:Epitopes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007121:Immunocompetence; D058965:MART-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000628:therapy; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D020218:Response Elements / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D058965:MART-1 Antigen