SBIR Phase II: Automated Closed Systems for Manufacturing Autologous Dendritic Cell Therapies

SBIR 第二阶段：用于制造自体树突状细胞疗法的自动化封闭系统

• 批准号: 1926967
• 负责人: Shashi Murthy
• 金额: $ 75万
• 依托单位: FLASKWORKS
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1926967&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Automated; Closed

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is in the development of new technologies to manufacture personalized therapies for cancer and other diseases, based on a patient's own cells. Such therapies have shown tremendous potential in the treatment of previously intractable cancers. However, challenges in manufacturing these completely personalized therapies are a significant impediment to the ability to realize their full societal potential both in terms of therapeutic efficacy and cost. This project aims to remove major manufacturing barriers for therapies based on dendritic cells, which are an important part of the human immune system and can be modified to target specific diseases. No manufacturing systems currently available can perform all the required steps of manufacturing personalized dendritic cell therapies. This project will address this major unmet need by leveraging advanced concepts in engineering and biology to design an integrated system for cost-effective dendritic cell therapy manufacturing. Given the large number of personalized cell-based therapies currently in clinical trials and recently approved, such a system is expected to address a major societal need and have significant commercial potential. This SBIR Phase II project will advance to commercialization an advanced bioreactor system for closed-system manufacturing of autologous dendritic cell therapies. Multiple technological challenges must be overcome to automate and integrate the unit operations associated with the manufacturing of these therapies. Because of their low abundance in blood and tissue, dendritic cells are typically generated from leukapheresis-derived monocytes. Adherent monocytes must first be converted into nonadherent immature dendritic cells via incubation inIL4 and GM-CSF, prior to maturation and stimulation with tumor specific antigens. In order to achieve automation and integration of these steps on a single platform, the proposed system will build on successful Phase I work in perfusion-based dendritic cell culture that enables reduction of process steps associated with cytokine infusion and achievement of perfusion in a simple and cost-effective single-use bioreactor design. In addition, an agile product development methodology will be utilized in conjunction with computational modeling to rapidly and iteratively create prototypes and test them in the hands of potential customers. Feedback obtained from these users will be incorporated into the assembly of a pre-production beta system to be launched commercially at the end of Phase II.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

小型企业创新研究(SBIR)第二阶段项目的更广泛影响/商业潜力是开发新技术，基于患者自己的细胞生产癌症和其他疾病的个性化疗法。这种疗法在治疗以前难以治愈的癌症方面显示出巨大的潜力。然而，在制造这些完全个性化的疗法方面的挑战是在治疗效果和成本方面充分发挥其社会潜力的能力的重大障碍。该项目旨在消除以树突状细胞为基础的疗法的主要制造障碍，树突状细胞是人类免疫系统的重要组成部分，可以针对特定疾病进行改造。目前还没有可用的制造系统可以执行制造个性化树突状细胞疗法所需的所有步骤。该项目将通过利用工程学和生物学中的先进概念来设计一种具有成本效益的树突状细胞治疗制造的集成系统，来解决这一尚未得到满足的主要需求。鉴于目前正在进行临床试验和最近获得批准的大量个性化细胞疗法，这样的系统有望满足主要的社会需求，并具有巨大的商业潜力。这个SBIR第二阶段项目将推进先进的生物反应器系统的商业化，用于闭合系统制造自体树突状细胞疗法。必须克服多项技术挑战，以实现与这些疗法的制造相关的单元操作的自动化和集成。由于其在血液和组织中的丰度较低，树突状细胞通常是从白细胞分离产生的单核细胞中产生的。在成熟和肿瘤特异性抗原刺激之前，贴壁的单核细胞必须首先通过IL4和GM-CSF的孵育转化为非贴壁的未成熟树突状细胞。为了在单一平台上实现这些步骤的自动化和集成，建议的系统将建立在基于灌流的树突状细胞培养的成功的第一阶段工作的基础上，该阶段能够减少与细胞因子输注相关的过程步骤，并在简单且具有成本效益的一次性生物反应器设计中实现灌流。此外，将利用敏捷的产品开发方法与计算建模相结合，快速迭代地创建原型，并在潜在客户手中测试它们。从这些用户那里获得的反馈将被合并到将在第二阶段结束时商业推出的试生产前测试版系统的组装中。该奖项反映了NSF的法定使命，并已通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。