SBIR Phase II: Clinical scale and testing of the first virus-free precision gene edited cell therapy for veterinary oncology

这个小企业创新研究（SBIR）二期项目的更广泛影响是开发一个商业化的细胞工程平台，这将使兽医市场上的癌症治疗成为可能。据估计，每年有25万只狗患上B细胞淋巴瘤。嵌合抗原受体(CAR)-T细胞疗法为治疗这种疾病提供了希望。大规模工程CAR-T细胞治疗的项目平台使兽医市场能够负担得起的潜在新治疗产品的产生。该项目潜在的社会和商业影响有可能将成功的狗疗法转化为人类癌症治疗。该解决方案还为人类制药行业的新型CAR-T细胞疗法的测试、开发和转化提供了一种新模式，可能对人类和狗都有好处。该项目解决了从研究阶段实验过渡到临床和商业阶段生产的主要瓶颈。在研究阶段，每个基因编辑实验或每个制造试点研究仅处理500万个CAR-T细胞的细胞工程平台就足够了。然而，要扩大到临床规模生产，并达到每年5万只狗的完全市场规模治疗，每次生产50-500剂的能力是必需的。规模化电穿孔系统可以处理多达500,000,000个细胞在一个单一的实验，从研究阶段系统增加了100倍。虽然细胞编程试剂的放大比例预计为1:100，但可能需要优化才能达到相同或更好的细胞编程效率，而这种细胞放大的下游产物也需要在小型生物反应器中进行优化。该提议的工程平台能够以低于500美元/剂的价格进行多达500剂CAR-T细胞疗法的工程设计。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 of this Small Business Innovation Research (SBIR) Phase II project is the development of a commercially-ready cell engineering platform that will enable a curative therapy for cancer in the veterinary market. An estimated 250,000 dogs get B cell lymphoma every year. Chimeric Antigen Receptor (CAR)-T cell therapy offers hope for a treatment for this disease. The project platform for engineering CAR-T cell therapy at scale enables the generation of a potential new therapeutic product that is affordable on the veterinary market. The potential societal and commercial impacts of the project have the potential to translate successful therapies from dogs into human cancer care. This solution also offers a new model for the testing, development, and translation of novel CAR-T cell therapies for the human pharmaceutical industry, potentially resulting in benefits to humans as well as dogs.This project addresses a major bottleneck in the transition from research phase experimentation to clinical and commercial phase manufacturing. During the research phase, cell engineering platforms that process only 5,000,000 CAR-T cells per gene editing experiment or per manufacturing pilot study are sufficient. However, to expand to clinical scale manufacturing and to reach full market scale treatment of 50,000 dogs per year, the ability to make 50-500 doses per manufacturing run is required. Scaled electroporation systems can process up to 500,000,000 cells in a single experiment, a 100x increase from the research phase system. While the scale-up in cell programming reagents is expected to be 1:100, optimization is likely to be required to reach the same or better cell programming efficiencies, while the downstream outgrowth of this scale-up of cells also needs to be optimized in small scale bioreactors. The proposed engineering platform enables engineering of up to 500 doses of CAR-T cell therapy for under $500/dose at full scale.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.