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

这一创新-技术转化伙伴关系(PFI-TT)项目的更广泛影响/商业潜力旨在为自然杀手(NK)免疫细胞制定有效、无毒的保存战略。NK疗法是由活细胞组成的，这些细胞在体外只能存活几小时或几天。如果没有冷冻保存，这些疗法只能在细胞收集和制造地点附近的有限数量的患者身上进行。随着NK细胞治疗试验的数量增加，包括治疗新冠肺炎的新兴临床试验，冷冻保存至关重要，以使这些挽救生命的疗法能够到达更多的患者手中。通过实现NK疗法的冷冻保存，拟议的NkCube产品将使这些疗法能够现成提供，并被运送到任何医院或诊所，从而使这种疗法得到更广泛的使用。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，从而允许批量生产的规模扩大，这反过来又可以降低这些疗法的成本。虽然传统疗法保存在有毒的溶液中，可能会导致危及生命的副作用，特别是在儿童和较小的患者中，但nkCube将使用对人类输液安全的分子配方。总体而言，拟议的nkCube技术旨在解决涉及NK疗法的安全性、质量和可获得性的问题，并将使更多的患者能够获得这些疗法。目前，NK细胞类型在体外只能存活几个小时。目前的NK保存方法在解冻后对肿瘤的杀伤作用较差，限制了治疗效果。为了实现产品与市场的匹配，该团队将解决客户发现过程中确定的关键障碍，包括需要优化NK细胞生存和功能的保存解决方案，需要设计与各种工作流程兼容的协议，以及需要对最终产品进行规模化制造和外部测试。该PFI-TT项目旨在将一种原型NK细胞防腐剂转化为满足NK细胞制造商需求的最低限度可存活的产品(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，并应该降低生产这类产品的总体成本。这项研究的成功结果将证明这一保护过程的概念证明。这一奖项反映了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 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.