72Figure: Study workflow: Data driven research for Atopic DermatitisFigure: Anti-tumor effects of CD19CAR iPS-NKTA) Direct cytotoxicity of CD19CAR iPS-NKT and wild-type iPS-NKT toward the CD19+ NALM-6 leukemia cell line. B) IFN-γ production by CD19CAR iPS-NKT and wild-type iPS-NKT cocultured with NALM-6 ± α-galactosylceramide-pulsed dendritic cells (DC/Gal).Animal Model DatabaseAnalyze for realizing personalized and preventive medicine for atopic dermatitisCross-sectional StudyGenomeTranscriptomePBMCSkin tissueLongitudinal StudyClinical Informationmanaged by “MeDIA”Human Atopic Dermatitis Databasedisorder. Although it has been suggested that an individual approach to each patient is crucial for understanding AD, suitable methods to do so have not been established yet. The purpose of this study, therefore, is to establish a method for disease clustering into sub-groups and to develop novel predictive treatment algo-rithms in each sub-group. To achieve this, we perform integrated analysis of genome and transcriptome data and multimodal clini-cal information from AD patients.In line with the above concept, we collected a large number of high-quality clinical samples in collaboration with Keio Uni-versity Hospital and established an integrated data analysis and repository infrastructure called the Medical Data Integration Assistant (MeDIA), which also enables us to conduct integrated studies with animal models. Analysis on cross-tissue ligand-receptor interactions by using transcriptomic analysis suggested augmented skin-PBMC crosstalk in AD patients compared to healthy subjects. We built a regression model that predicts clinical phenotypes of AD with transcriptome modules generated by ap-plying weighted gene co-expression network analysis on RNA-seq data of skin and PBMC. We identified differential immunological peutic potential in many areas, including regenerative medi-cine and immune therapy. On a collaborative basis with individ-ual IMS research laboratories, the core facility for iPS research is aiming to put cancer immunotherapy with iPS-derived NKT cells into clinical use.The facility has operated an IMS Cell Manufacturing Unit (CMU) to produce iPS-derived human invariant NKT (Vα24+iNKT) cells under GMP (Good Manufacturing Practice)/GCTP (Good Gene, Cellular, and Tissue-based Products Manu-facturing Practice) guidelines. The safety of these iPS-Vα24+iNKT cells was confirmed by preclinical studies. The facility had fin-ished PMDA (Pharmaceuticals and Medical Devices Agency) consultation for clinical trials of iPS-Vα24+iNKT cell-mediated signatures associated with two distinctive skin manifestations of AD. Longitudinal tissue transcriptomic data analysis of patients treated with molecularly-targeted therapies also revealed charac-teristics of each patient’s genetic profile that were associated with differences in treatment response.Our approach will not only pave the way toward realization of personalized preventive medicine for AD, but also for develop-ment of new technologies in data-driven medical research, and therefore will have a considerable impact on society.head and neck cancer immunotherapy and has been conducting the clinical trial. The facility is also preparing another clinical trial on combination therapy with iPS-Vα24+iNKT cells and dendritic cells for head and neck cancer, and it will be started in the next year.Currently, to maximize the efficacy of iPS-Vα24+iNKT cells, activation with dendritic cells is mandatory and it might complicate the treatment. However, if direct activation of iPS-Vα24+iNKT cells can be accomplished, treatment with fully acti-vated iPS-Vα24+iNKT cells will be easily achieved. To implement this direct activation, the facility focused on Chimeric Antigen Receptor (CAR) introduction into iPS-Vα24+iNKT cells. Among several CARs, the facility chose CD19 and CD25 CARs to treat leukemia and has now been conducting a proof of concept study.iPS ProjectInduced pluripotent stem (iPS) cells possess tremendous thera-Data-Driven Research for Atopic DermatitisAtopic dermatitis (AD) is a heterogeneous and multifactorial
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