title: Efficient priming and expansion of antigen-specific CD8+ T cells by a novel cell-based artificial APC.
abstract: The ex vivo priming and expansion of human CTL by APC, such as autologous monocyte-derived dendritic cells (DC), has the potential for use in immunotherapy for infectious diseases and cancer. To overcome the difficulty of obtaining sufficient number of autologous DC from patients, we have developed cell-based artificial APC (aAPC), designated Med-APC. These aAPC rapidly activate and expand the corresponding Ag-specific CD8+ T cells when pulsed with CTL epitope peptide(s) as efficiently as mature DC (mDC). We have also shown that Med-APC possess an innate cellular machinery that is sufficient to support the processing of complete Ag into immunodominant peptides, which considerably extends the usefulness of this technology. In addition, we have developed a novel expression vector system that expresses ubiquitinated Ag, resulting in an enhanced APC function of this system. Genetically encoded Ag can be easily introduced into Med-APC by transfection with this vector. Med-APC transfected with ubiquitinated Ag can efficiently expand the corresponding Ag-specific CTL without exogenous peptides. Therefore, Med-APC may have important therapeutic implications for adoptive immunotherapy and can be used for the detection of Ag-specific CTL for immunomonitoring.
authors.affiliation: Medinet Medical Institute, Medinet Co. Ltd, Tamagawadai, Japan.
authors.forename: Shigemi
authors.initials: S
authors.lastname: Sasawatari
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Tadaki
authors.forename: Manami
authors.initials: M
authors.lastname: Isogai
authors.forename: Masashi
authors.initials: M
authors.lastname: Takahara
authors.forename: Mie
authors.initials: M
authors.lastname: Nieda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kakimi
mesh_terms: D000938:Antigen-Presenting Cells / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005822:Genetic Vectors; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D058965:MART-1 Antigen; D009363:Neoplasm Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D025801:Ubiquitin / Q000235:genetics; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010750:Phosphoproteins; C090236:SM protein, Human herpesvirus 4; D015534:Trans-Activators; D025801:Ubiquitin; D014764:Viral Proteins; D007371:Interferon-gamma