CLINICAL SCALE EXPANSION OF HUMAN DENDRITIC CELLS

描述（改编自申请人摘要）：树突状细胞 (DCS)是高度特化的骨髓源性抗原呈递 细胞（APC），其作为T细胞的有效刺激细胞起作用。 淋巴细胞介导的免疫反应。树突状细胞免疫治疗 是涉及离体扩增的新兴治疗策略， 将抗原脉冲的DCS再输注到人类患者中以进行疫苗接种 对抗癌症或传染病。这方面的一个主要限制是， 方法是能够产生足够数量的 功能DCS，用于有效的患者治疗。的主要目的 拟议的研究是制定和实施一个独特的过程， 离体扩增、分化、肿瘤抗原加载和收获 的DCS在连续灌注临床规模的生物反应器系统。的 假设连续单程培养基交换将使得 在Aastrom细胞中以高密度增强功能DCS的生产 将测试生产系统（CPS）。第二阶段计划将重点 在优化和完全自动化的过程中， GMP法规。该自动化系统将在临床试验中进行测试 评估CPS中产生的树突状细胞的安全性和有效性， 用于人癌胚抗原（CEA）特异性癌症治疗。一个 自动化临床规模的生物反应器系统将能够实现高效的 作为上级APC类型的高功能树突状细胞的产生 癌症免疫疗法 拟定商业应用： 用于树突状细胞扩增的封闭式自动GMP系统， 分化、抗原加载和收获对于本领域技术人员来说将是非常有价值的。 癌症和传染病的免疫治疗。现有方法 树突状细胞扩增涉及多个开放的过程步骤， 设备和劳动力的相关成本。开发基于CPS的 直流扩容工艺将使成功的 树突状细胞疗法以可靠和具有成本效益的方式。

DESCRIPTION (Adapted from the applicant's abstract): Dendritic cells (DCS) are highly specialized bone marrow-derived antigen presenting cells (APCs) which function as potent stimulating cells for T- lymphocyte-mediated immune responses. Dendritic cell-based immunotherapy is an emerging treatment strategy involving ex vivo expansion and reinfusion of antigen-pulsed DCS into human patients to vaccinate against cancer or infectious diseases. A major limitation in this approach has been the capability to generate sufficient quantities of functional DCS for effective patient therapy. The primary objective of the proposed studies is to develop and implement a unique process for ex vivo expansion, differentiation, tumor antigen-loading and harvest of DCS in a continuously perfused clinical-scale bioreactor system. The hypothesis that continuous single-pass medium exchange will enable enhanced production of functional DCS at high density in Aastrom's Cell Production System (CPS) will be tested. The Phase II program will focus on optimization and full automation of the process in compliance with GMP regulations. The automated system will be tested in clinical trials to assess the safety and efficacy of dendritic cells produced in the CPS for human carcino-embryonic antigen (CEA-specific cancer therapy. An automated clinical scale bioreactor system would enable efficient production of highly functional dendritic cells as a superior APC type for cancer immunotherapy. PROPOSED COMMERCIAL APPLICATION: A closed, automated, GMP system for dendritic cell expansion, differentiation, antigen-loading and harvest would be of great value for immunotherapy of cancer and infectious diseases. The existing methods for dendritic cell expansion involve multiple open process steps with associated costs in equipment and labor. The development of a CPS-based DC expansion process will enable widespread application of successful dendritic cell-based therapies in a reliable and cost-effective fashion.