title: Quality controls in cellular immunotherapies: rapid assessment of clinical grade dendritic cells by gene expression profiling.
abstract: Cell-based immunotherapies are among the most promising approaches for developing effective and targeted immune response. However, their clinical usefulness and the evaluation of their efficacy rely heavily on complex quality control assessment. Therefore, rapid systematic methods are urgently needed for the in-depth characterization of relevant factors affecting newly developed cell product consistency and the identification of reliable markers for quality control. Using dendritic cells (DCs) as a model, we present a strategy to comprehensively characterize manufactured cellular products in order to define factors affecting their variability, quality and function. After generating clinical grade human monocyte-derived mature DCs (mDCs), we tested by gene expression profiling the degrees of product consistency related to the manufacturing process and variability due to intra- and interdonor factors, and how each factor affects single gene variation. Then, by calculating for each gene an index of variation we selected candidate markers for identity testing, and defined a set of genes that may be useful comparability and potency markers. Subsequently, we confirmed the observed gene index of variation in a larger clinical data set. In conclusion, using high-throughput technology we developed a method for the characterization of cellular therapies and the discovery of novel candidate quality assurance markers.
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Luciano
authors.initials: L
authors.lastname: Castiello
authors.forename: Marianna
authors.initials: M
authors.lastname: Sabatino
authors.forename: Yingdong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Barbara
authors.initials: B
authors.lastname: Tumaini
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Ren
authors.forename: Jin
authors.initials: J
authors.lastname: Ping
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.forename: Lauren V
authors.initials: LV
authors.lastname: Wood
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Raj K
authors.initials: RK
authors.lastname: Puri
authors.forename: David F
authors.initials: DF
authors.lastname: Stroncek
mesh_terms: D002454:Cell Differentiation; D019295:Computational Biology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D046228:Microarray Analysis; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D011786:Quality Control