I-Corps: Chimeric Antigen Receptor T Cell Manufacturing for Cancer Therapies

这个i-Corps项目的更广泛的影响/商业潜力是开发一种离心式流态化膨胀生物反应器，即一种细胞制造设备，它可以缩短生产时间，培养用于癌症治疗的免疫细胞。癌症免疫疗法在临床试验研究中显示出巨大的前景和疗效，其中7种已被食品和药物管理局(FDA)批准；然而，制造这些细胞仍然是广泛采用的限制因素。目前FDA批准的疗法每次输液需要多达2.5亿个免疫细胞，单剂成本接近50万美元。目前的制造限制强调了在单元制造中创新的迫切需要。之前对动物模型的研究表明，与市场上最快的技术相比，这种解决方案可以将细胞疗法的制造时间减少30%。使用这项技术，生物制药公司的制造总监可能能够节省设施中的空间，并节省劳动力和细胞培养资源的资金，而癌症中心的临床医生能够以更快的速度治疗患者。通过解决时间和资源限制，这项技术有可能减少挽救生命的细胞疗法的经济障碍，从而增加癌症患者的采用率。这个i-Corps项目是基于离心式流态化膨胀灌流生物反应器原型的开发。与目前的解决方案不同，该生物反应器通过平衡离心力和连续喂入新鲜介质来去除抑制性废物并保留细胞，从而简化了细胞扩张过程。早期研究表明，牛的免疫细胞可以扩大，原型可以维持超过1亿个细胞/毫升的高细胞密度，将制造时间从7-14天缩短到5天，并将细胞生长保持在最大速率的95%。此外，与目前的制造设备不同，生物反应器可以很容易地安装在标准的实验室工作台上，并且完全自给自足，其外壳作为一个独立的单元，带有空气过滤器和紫外线-C杀菌--消除了对数百万美元洁净室的需要。以前的研究结果支持该设备将对癌症细胞治疗的可扩展性和可获得性产生的潜在影响。该奖项反映了NSF的法定使命，并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。

The broader impact/commercial potential of this I-Corps project is the development of a centrifugal fluidized expansion bioreactor, i.e., a cell manufacturing device, that reduces the production time to grow immune cells for cancer treatment. Cancer immunotherapies have shown great promise and efficacy in clinical trial studies, with seven being approved by the Food and Drug Administration (FDA); However, manufacturing these cells remains a limiting factor in widespread adoption. Current FDA-approved therapies require up to 250 million immune cells per infusion, with costs for a single dose nearing $500,000. The current manufacturing limitations underscore the urgent need for innovation in cell manufacturing. Prior research with an animal model shows this solution can reduce the manufacturing time for cell therapies by 30% in comparison to the fastest technology on the market. Using this technology, manufacturing directors at biopharmaceutical companies may be able to save space in their facilities and save money on labor and cell culture resources while clinicians at cancer centers are able to treat patients at a faster rate. By addressing time and resource limitations, the technology has the potential to reduce the financial barrier to lifesaving cell therapies, increasing adoption by cancer patients. This I-Corps project is based on the development of a centrifugal fluidized expansion perfusion bioreactor prototype. The bioreactor streamlines the cell expansion process by balancing centrifugal forces with a continuous feed of fresh medium to remove inhibitory waste products and retain cells unlike current solutions. Early research has shown that immune cells from cattle can be expanded, and that the prototype can sustain high cell population densities over 100 million cells/mL, reducing manufacturing time from 7-14 days to 5 days, and maintaining cell growth at 95% of the maximum rate. Moreover, unlike current manufacturing equipment, the bioreactor fits easily on a standard lab bench and is entirely self-contained, with its housing acting as a standalone unit with air filters and ultraviolet-c sterilization—eliminating the need for multi-million dollar cleanrooms. Findings from prior research support the potential impact the device would have on scalability and accessibility of cancer cell therapies.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.