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

SBIR II 期：第一个用于兽医肿瘤学的无病毒精准基因编辑细胞疗法的临床规模和测试

• 批准号: 2243587
• 负责人: Wesley Wierson
• 金额: $ 97.39万
• 依托单位: LIFENGINE ANIMAL HEALTH LABORATORIES INCORPORATED
• 依托单位国家: 美国
• 项目类别: Cooperative Agreement
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-10-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2243587&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Clinical; scale

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.

这个小型企业创新研究(SBIR)第二阶段项目的更广泛影响是开发了一个商业化的细胞工程平台，将使兽医市场上的癌症根治成为可能。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细胞疗法为这种疾病的治疗带来了希望。规模化设计CAR-T细胞治疗的项目平台使潜在的新治疗产品的产生成为可能，这种治疗产品在兽医市场上是负担得起的。该项目的潜在社会和商业影响有可能将狗的成功疗法转化为人类癌症护理。该解决方案还为人类制药业的新型CAR-T细胞疗法的测试、开发和翻译提供了一种新的模式，潜在地为人类和狗带来好处。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生产先导研究只处理500万个CAR-T细胞的细胞工程平台就足够了。然而，为了扩大到临床规模的生产，并达到每年50,000只狗的完全市场规模治疗，需要有每次生产50-500剂的能力。规模化电穿孔系统在一次实验中可以处理多达500,000,000个细胞，比研究阶段的系统增加了100倍。虽然单元编程试剂的规模预计为1：100，但很可能需要进行优化才能达到相同或更好的单元编程效率，而这种单元规模扩大的下游产物也需要在小型生物反应器中进行优化。拟议的工程平台能够以低于500美元/剂量的价格全面设计高达500剂的CAR-T细胞疗法。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。