PFI-TT: Developing next-generation cryopreservation media for natural killer cells

这个创新-技术转化伙伴关系（PFI-TT）项目的更广泛的影响/商业潜力寻求产生一种有效的、无毒的自然杀伤（NK）免疫细胞保存策略。NK疗法由活细胞组成，这些活细胞只能在体外存活数小时或数天。如果没有低温保存，这些疗法只能用于数量有限的靠近细胞收集和制造部位的患者。随着NK细胞治疗试验数量的增加，包括新出现的治疗COVID-19的临床试验，冷冻保存对于让这些拯救生命的疗法惠及更多的患者至关重要。通过冷冻保存NK疗法，提议的nkCube产品将使这些疗法成为现成的，并运送到任何医院或诊所，从而使这种疗法得到更广泛的应用。nkCube的无毒配方也将促进NK疗法的发展。细胞将在溶液中稳定几个小时，允许批量生产的规模扩大，这反过来可以降低这些治疗的成本。传统疗法保存在有毒溶液中，可能导致危及生命的副作用，特别是对儿童和体型较小的患者，而nkCube将采用安全的分子配制，可用于人体输注。总的来说，拟议的nkCube技术旨在解决涉及NK疗法的安全性、质量和可用性的问题，并使这些疗法能够为更多的患者所接受。目前，NK细胞只能在体外存活几个小时。目前的NK保存方法导致解冻后肿瘤杀伤功能差，限制了治疗的有效性。为了实现产品市场契合，该团队将解决客户发现过程中发现的关键障碍，包括优化NK细胞存活和功能的保存解决方案的需求，设计与各种工作流程兼容的协议的需求，以及执行规模制造和最终产品外部测试的需求。该PFI-TT项目旨在将NK细胞防腐剂原型转化为满足NK细胞制造商需求的最小可行产品（nkCube）。更好的保存这些细胞的方法可能有助于细胞的生物制造，并应降低生产此类产品的总体成本。这项研究的成功结果将证明这一保存过程的概念。该奖项反映了美国国家科学基金会的法定使命，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 Partnerships for Innovation - Technology Translation (PFI-TT) project seeks to produce an effective, non-toxic preservation strategies for natural killer (NK)immune cells. NK therapies are composed of living cells that survive for only hours or days outside the body. Without cryopreservation, these therapies can only be administered to a limited number of patients close to the sites of cell collection and manufacturing. As the number of NK cell therapy trials grows, including emerging clinical trials to treat COVID-19, cryopreservation is essential to allow these life-saving therapies to reach a larger number of patients. By enabling cryopreservation of NK therapies, the proposed nkCube product would allow these therapies to be made available off-the-shelf and transported to any hospital or clinic, enabling wider use of this therapy. The nontoxic formulation of nkCube will also facilitate the growth of NK therapies. Cells will be stable in the solution for several hours, allowing for scale-up in batch production, which in turn could decrease the cost of these therapies. While traditional therapies are preserved in a toxic solution that can cause life-threatening side effects, especially in children and smaller patients, nkCube will be formulated with molecules that are safe for human infusion. Overall, the proposed nkCube technology aims to address issues involving the safety, quality and availability of NK therapies, and would allow these therapies to be accessible to a larger population of patients.Currently, the NK cell type survives for only a few hours outside of the body. Current methods of NK preservation result in poor post-thaw tumor killing function, which limits the effectiveness of the treatment. In order to achieve product-market fit, the team will address key hurdles identified in the customer discovery process, including the need to optimize a preservation solution for NK cell survival and function, the need to design a protocol compatible with a variety of workflows, and the need to perform scaled manufacturing and external testing of the final product. This PFI-TT project aims to translate a prototype NK cell preservative into a minimum viable product (nkCube) that meets the needs of NK cell manufacturers. Better methods of preserving these cells may aid in the biomanufacturing of the cells and should reduce the overall cost of producing this type of product. A successful outcome of this study will demonstrate the proof of concept for this preservation process.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.