3-Laser Flow cytometer

在新任命的背景下，我们计划通过几项新活动进一步扩大我们的“细胞治疗”计划。我们希望建立临床前研究，并在此研究计划的基础上启动临床I/II期试验。现有的GMP实验室基础设施，内科II的强大的患者项目和我们完善的GCP研究中心（目前有60个活跃的临床试验和300名患者/年）将为建立这个转化研究项目提供实质性的支持。为了实现项目的转化研究部分，以下两种主要研究仪器是强制性的，因此在本申请中申请：(1)用于临床试验患者的符合gmp的细胞疗法生产的仪器，带有封闭系统中的额外电穿孔器(例如，异体NK细胞，iNKT细胞，(2)流式细胞仪，用于分析生产的细胞产物和监测免疫细胞及其对免疫系统的影响（免疫监测）以及对体内肿瘤细胞的影响（例如，包括最小残留疾病的量化）。在未来几年内，这两种主要研究仪器将用于生产细胞产品并进行相关研究，例如以下临床试验：mb - art - bcma /CD19在晚期多发性骨髓瘤患者中的I/II期剂量发现和疗效研究”（单中心，单臂，I/II期研究，由<s:1>宾根医学院（AKF项目）资助）；PI: b.b esemer/ Co-PI w.b Bethge)。“MB-CART-CD19/CD22在晚期淋巴细胞恶性肿瘤患者中的I/II期剂量发现和疗效研究”（单中心，单臂，I/II期研究，在<s:1>宾根医学院（AKF项目）申请财政支持，PI: W. Bethge/ Co-PI C. Lengerke）。自然杀伤细胞免疫疗法联合parp抑制克服nkg2d介导的急性髓性白血病（NAKIP-AML）的免疫逃避；三中心I/II期研究，PI t<s:1>宾根：Claudia Lengerke； t<s:1>宾根和德累斯顿：异体NK细胞制造中心；该研究基于Lengerke教授研究小组产生的临床前数据，参见Paczulla，…, Lengerke。自然,2019;这项研究已经获得了NCT的资助。4 .与(3)类似，用于高风险AML的同种异体移植后的巩固（研究在准备中，PI: C. Lengerke/ Co-PI: D. Schneidawind）。iNKT细胞和用于移植物抗宿主病和其他免疫疾病的其他细胞疗法（研究方案正在准备中，PI: D. Schneidawind/Co-PI: R. Haraszti）

In the context of a new appointment we plan to further expand our “Cell Therapy” program by several new activities. We wish to build preclinical research and initiate, based on this research program, clinical phase I/II trials. The already existing GMP lab infrastructures, the robust patient programs of the Internal Medicine II and our well-established GCP Study Center (currently >60 active clinical trials and 300 patients/year) will provide substantial support to establish this translational research program.To enable the translational research part of the program, following two Major Research Instruments are mandatory and thus applied for in this application:(1) an instrument for GMP-compliant production of cell therapies for application in patient in clinical trials, with an additional electroporator in closed system (e.g., allogeneic NK cells, iNKT cells, CAR-T cells) and(2) a flow cytometer for the analysis of the produced cellular products and the monitoring of the immune cells and their effect on the immune system (immunomonitoring) as well as on the tumor cells in vivo (e.g., including quantification of the minimal residual disease).Within the next years, both Major Research Instrument will be used to generate cellular products and to perform the accompanying research for example for the following clinical trials:1. „A phase I/II dose finding and efficacy study of MB-CART-BCMA/CD19 in patients with advanced multiple myeloma“ (single-center, single-arm, phase I/II study, financial support awarded by the Medical Faculty Tübingen (AKF program), ; PI: B. Besemer/ Co-PI W. Bethge).2. “A phase I/II dose finding and efficacy study of MB-CART-CD19/CD22 in patients with advanced lymphoid malignancies” (single-center, single-arm, phase I/II study, financial support applied for at the Medical Faculty Tübingen (AKF program), PI: W. Bethge/ Co-PI C. Lengerke).3. „Natural Killer Cell Immunotherapy in combination with PARP-inhibition to overcome NKG2D-mediated immune evasion in Acute Myeloid Leukemia“ (NAKIP-AML; triple-center phase I/II study, PI Tübingen: Claudia Lengerke; Tübingen und Dresden: manufacturing centers for allogeneic NK cells; the study is based on pre-clinical data generated in the research group of Prof. Lengerke, see Paczulla,..., Lengerke. Nature, 2019; study has been awarded funding by the NCT)4. Similar as in (3) for consolidation after allogeneic transplantation at high risk AML (study in preparation, PI: C. Lengerke/ Co-PI: D. Schneidawind)5. iNKT cells and additional cellular therapies concerning graft-versus-host disease and other immunological diseases (study protocol in preparation, PI: D. Schneidawind/Co-PI: R. Haraszti)