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

该I-Corps项目更广泛的影响/商业潜力是开发离心流化膨胀生物反应器，即，一种细胞制造设备，它减少了用于癌症治疗的免疫细胞生长的生产时间。癌症免疫疗法在临床试验研究中显示出巨大的前景和功效，其中七种已获得美国食品和药物管理局（FDA）的批准;然而，制造这些细胞仍然是广泛采用的限制因素。目前FDA批准的疗法每次输注需要多达2.5亿个免疫细胞，单剂量的成本接近50万美元。目前的制造限制强调了对电池制造创新的迫切需要。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缩短30%。使用这项技术，生物制药公司的生产主管可以节省设施空间，节省劳动力和细胞培养资源，而癌症中心的临床医生则能够以更快的速度治疗患者。通过解决时间和资源限制，该技术有可能减少挽救生命的细胞疗法的财务障碍，增加癌症患者的采用。该I-Corps项目是基于离心流化膨胀灌注生物反应器原型的开发。生物反应器通过平衡离心力与新鲜培养基的连续进料来简化细胞扩增过程，以去除抑制性废物并保留细胞，这与当前的解决方案不同。早期的研究表明，来自牛的免疫细胞可以扩增，原型可以维持超过1亿个细胞/mL的高细胞群密度，将制造时间从7-14天减少到5天，并保持细胞生长在最大速率的95%。此外，与目前的生产设备不同，生物反应器可以很容易地安装在标准的实验室工作台上，并且是完全独立的，其外壳作为一个独立的单元，带有空气过滤器和紫外线c消毒，从而消除了对数百万美元的洁净室的需求。先前的研究结果支持该设备对癌细胞治疗的可扩展性和可及性的潜在影响。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值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.