Clinical grade cell separation technologies in the Newcastle Cellular Therapies Facility

作为药物的细胞的生产是一个受监管的过程，只能按照制造程序、质量控制程序和欧盟指令在获得许可的场所进行。纽卡斯尔大学和纽卡斯尔对泰恩NHS基金会信托基金进行了必要的基础设施投资，以建造、维护和许可符合良好制造规范(GMP)的生产设施。制造细胞作为药物的必要许可证已经获得，皇家维多利亚医院的临床试验单位和弗里曼医院的移植研究所通过为细胞治疗患者提供特定床位来为患者提供临床支持。纽卡斯尔细胞疗法机构目前正在进行两项细胞疗法的临床试验。第一个是与Francisco Figuieredo教授进行的MRC自体角膜缘干细胞治疗眼外伤的试验，第二个是与John Isaacs教授进行的致耐受树突状细胞(TolDC)治疗类风湿关节炎的试验。此外，HTA已经批准与斯蒂芬·怀特教授进行自体胰岛细胞治疗。此外，迪金森教授是造血干细胞移植实验室的主任，该实验室目前负责每年向患有恶性血液疾病和免疫缺陷的成人和儿科患者发放约400种细胞治疗产品。NCTF雇用了一批具有实践、科学和监管专业知识的合格工作人员，他们能够发起和开发用于细胞疗法临床试验的产品。NCTF接受MHRA、HTA和内部审计的检查。受雇的员工包括一名药房合格人员、一名质量保证经理和健康专业委员会注册的生物医学科学家，他们与临床医生和临床试验团队密切合作。AIMS和OBJECTIVES我们通过MRC再生医学资本资助计划寻求支持，用于购买设备，这些设备将安装在GMP生产洁净室内，这些洁净室有能力通过细胞表面标记的表达来净化细胞群体。与磁珠结合的抗体允许选择或耗尽选定的细胞类型，这是一项成熟的技术。Miltenyi-Biotec生产两种不同的机器或平台，可以利用磁珠技术来净化细胞群。第一种是Clinimacs Plus，它使用磁珠，但设计用于将选定的细胞净化到无菌袋中，然后可以发放准备输液或进一步操作。第二个是新的Clinimacs Prodigy，它提供了一个封闭的工作站，能够以可编程的方式处理、纯化和培养细胞，并可以为其设计和优化特定的过程。这是一项最先进的技术，可用于细胞疗法的新工艺开发和临床级制造。ApplicATIONS&BENEFITSTHE Clinimacs Plus将支持TolDC试验。Clinimacs Prodigy将立即用于新方案的开发，利用我们与伊娃·韦辛格教授领导的汉诺威小组的合作，为在异基因骨髓输注后感染CMV的患者进行病毒特异性T细胞治疗。Miltenyi-Biotec设计的方案使神童适合和可行于这项研究。因此，所要求的设备将使NCTF有能力帮助当前的临床试验和新临床试验的研究，并开发新的细胞治疗方案，以满足MRC战略。此外，随着迪金森教授参与欧盟资助的建立细胞治疗标准的倡议，以支持多中心试验的一致性，我们将在我们的设施中托管该设备，从而支持整个欧盟在细胞治疗制造方面的研究、教学和培训。

CONTEXTThe production of cells as medicines is a regulated process and can only be conducted in accordance with manufacturing procedures, quality control processes, and in licensed premises according to EU Directives. Newcastle University and Newcastle upon Tyne NHS Foundation Trust have invested in the necessary infrastructure to build, maintain and license production facilities compliant with Good Manufacturing Practice (GMP). The necessary licenses for manufacturing cells as medicines have been obtained, and with the Clinical Trials Unit at the Royal Victoria Infirmary and the Institute for Transplantation at the Freeman Hospital, clinical support for patients is enabled by the provision of specific beds for cell therapy patients. The Newcastle Cellular Therapies Facility is currently running two clinical trials in cellular therapies. The first is the MRC Autologous Limbal Stem Cell trial for eye trauma with Professor Francisco Figuieredo, and the second is the tolerogenic dendritic cell (TolDC) trial for rheumatoid arthritis with Professor John Isaacs. In addition, HTA approval has been granted for autologous pancreatic islet cell therapy with Professor Stephen White. Furthermore, Professor Dickinson is Director of the Haematopoietic Stem Cell Transplant laboratory which is currently responsible for releasing approximately 400 cell therapy products per year to adult and paediatric patients suffering from malignant blood disorders and immune deficiency. A number of qualified staff with practical, scientific and regulatory expertise are employed within the NCTF who are able to initiate and develop products for clinical trials in cellular therapies. The NCTF is subjected to inspections by the MHRA, HTA and internal audits. The staff employed include a Pharmacy Qualified Person, a Quality Assurance Manager, and Health Professional Council-registered Biomedical Scientists who work closely with clinicians and clinical trial teams.AIMS AND OBJECTIVESWe seek support through the MRC Regenerative Medicine Capital Funding scheme for the purchase of equipment to be housed within the production GMP cleanrooms that have the capacity to purify populations of cells by their expression of cell surface markers. Antibodies conjugated to magnetic beads that permit the selection or depletion of chosen cell types is established technology. Miltenyi-Biotec produces two different machines, or platforms, that can exploit the magnetic bead technology to purify cell populations. The first is the Clinimacs Plus that uses magnetic beads but is designed to purify chosen cells into sterile bags that can then be issued ready for infusion or further manipulation. The second is the new Clinimacs Prodigy that offers a closed workstation capable of processing and purifying and culturing cells in a programmable way and for which specific processes can be designed and optimised. It is state-of-the-art technology that can be used for new process development as well as clinical grade manufacturing of cell therapies.APPLICATIONS & BENEFITSThe Clinimacs Plus would support the TolDC trial. The Clinimacs Prodigy will find immediate use in development of new protocols, exploiting our collaboration with the Hannover group led by Professor Eva Weissinger, for virus-specific T-cell therapy in patients who contract CMV after allogeneic bone marrow infusions. Protocols designed by Miltenyi-Biotec render the Prodigy appropriate and feasible for this research. The equipment requested will therefore give NCTF the capacity to aid current clinical trials and research into new clinical trials, and develop new protocols in cell therapy to meet the MRC strategy. In addition, research, teaching and training in cell therapy manufacture will be supported across the EU by hosting this equipment in our facility as Professor Dickinson participates in EU funded initiatives to establish standards in cell therapy to support consistency across multi-centre trials.