SBIR Phase I: Ratcheting Cytometry Instrument for Performing Cell Therapy Quality Control Assays

这个小型企业创新研究(SBIR)项目的更广泛影响/商业潜力将是开发一种工具，以解决质量控制的规模和监管挑战，这些挑战增加了成本，阻碍了细胞疗法在广泛的患者基础上的大规模部署。利用人类基因工程细胞的细胞疗法已经显示出令人难以置信的潜力，它是实现癌症患者个性化治疗的“活药”。最近这些疗法的改进表明，它们在靶向和杀死特定类型的白血病方面有效。鉴于这些成功，越来越多的研究和临床试验被提出，以提高目前治疗血癌的疗效，并使这些治疗方法适应其他类型的癌症。尽管在抗击癌症方面表现出了希望，但人们越来越关注临床剂量的可制造性，特别是在扩大规模以满足全球需求的时候。此外，这些疗法的开发速度正在导致监管机构在质量控制和释放标准方面落后。随着细胞疗法的不断改进和需求的增加，这两个问题都需要解决。这个SBIR第一阶段项目建议开发一种用于细胞疗法制造的综合质量控制工具，该工具以一种名为棘轮细胞术的颠覆性新技术为中心。目前，治疗细胞批次的质量控制仍然很难标准化和规模化，因为需要过多的独立工具来充分表征每一批。这种模块化方法资本成本高，经常性维护成本高，需要熟练的技术人员。理想情况下，这些独立工具的功能可以合并到一个自动化系统中，以提供标准化的细胞治疗质量指标，而不会出现用户变异性。利用成熟的免疫磁性细胞标记技术，棘轮细胞术能够通过单独测量磁含量和基于表面表达的门控来结合质量控制工具的功能。利用这些优势，目标是证明一种综合仪器的可行性，以在一步测试中量化治疗细胞批次的细胞数量、活性、表面表达和细胞因子分泌。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be the development of an instrument to address the scaling and regulatory challenges of quality control that increase cost and impede large scale deployment of cellular therapies to a wide patient base. Cellular therapies taking advantage of engineered human cells have shown incredible potential as "living drugs" that achieve personalized therapies for cancer patients. Recent improvements in these therapies have shown their efficacy in targeting and killing specific types of leukemias. In light of these successes, more and more research and clinical trials are being proposed to improve current efficacy in treating blood cancers and adapting these therapies to other cancers types. While showing promise in the fight against cancer, there is growing concern over the manufacturability of clinical doses, especially when scaling up to meet global demands. Additionally, the speed at which these therapies are being developed is causing regulatory agencies to lag behind in terms of quality control and release criteria. Both of these issues will need to be addressed as cellular therapies continue to improve and increase in demand. This SBIR Phase I project proposes to develop an integrated quality control instrument for the manufacture of cellular therapies, which centers around a disruptive new technology called ratcheting cytometry. Currently, quality control of therapeutic cell batches remains difficult to standardize and scale given the plethora of standalone tools needed to adequately characterize each batch. This modular approach has high capital cost, high recurring maintenance costs, and requires skilled technicians. Ideally, the capabilities of these standalone tools can be combined into one automated system to provide standardized metrics for cellular therapy quality without user variability. Leveraging well-established immunomagnetic cell labeling techniques, ratcheting cytometry is able combine the capabilities of quality control tools by individually measuring magnetic content and gating based on surface expression. Leveraging these advantages, the goal is to demonstrate feasibility for an integrated instrument to quantify cell number, viability, surface expression, and cytokine secretion of therapeutic cell batches in a single step assay.