Rapid, single-step precision engineering and pre-clinical evaluation of chimeric antigen receptor Regulatory T cells for Type 1 diabetes

患者来源的调节性T(Treg)细胞的体外工程有望成为一种安全有效的方法 用于治疗1型糖尿病(T1D)。尽管临床前研究前景看好，但相当大的生物学和技术 在实现这一治疗策略之前，必须解决障碍。首先，必须对Treg细胞进行改造 以最佳方式增强其特异性、稳定性和功能性。第二，可伸缩性问题--或生成 必须克服足够的患者来源的体外工程细胞的产量来构成治疗剂量。 因迪。Inc.正在用他们的HADPOLE™平台应对所有这些挑战。水孔™使用天然的 正在发生的流体动力学现象-涡流脱落-使Treg细胞工程能够增强 与使用基于病毒的当前黄金标准相比，在更短的时间内解决稳定性、功能性和可扩展性问题 方法和电穿孔。AquporeTM最终产生了更有效的工程T细胞，如Tregs。 在这份提案中，Indee。Inc.将在下一步工程中展示HodPore™的技术性能 T1D嵌合抗原受体调节性T细胞(CAR-Tregs)的制备研究还将重点放在 展示了利用AquporeTM基因工程的CAR-Tregs优越的体内外生物学活性 相对于那些使用传统方法设计的。在成功完成这些目标之前， CAR-Tregs将使用从T1D患者分离的Treg细胞进行工程设计，并展示临床和 商业规模的加工和浓缩足够的Car-Tregs细胞用于人体试验。

Ex vivo engineering of patient-derived regulatory T (Treg) cells holds promise as a safe and effective approach for treating type 1 diabetes (T1D). Despite promising preclinical studies, considerable biological and technical hurdles must be addressed before this therapeutic strategy can be realized. First, Treg cells must be engineered to optimally enhance their specificity, stability, and functionality. Second, scalability issues – or generating sufficient yield of patient-derived, ex vivo engineered cells to constitute a therapeutic dose – must be overcome. Indee. Inc. is addressing all of these challenges with their Hydropore™ platform. Hydropore™ uses a naturally occurring fluid dynamics phenomenon – vortex shedding – to enable Treg cell engineering that enhances the stability, functionality, and scalability issues in less time than the current gold standards that use virus-based methods and electroporation. HydroporeTM ultimately results in more effective engineered T cells such as Tregs. In this proposal, Indee. Inc. will demonstrate the technical performance of Hydropore™ in engineering the next generation of chimeric antigen receptor regulatory T cells (CAR-Tregs) for T1D. Studies will also focus on demonstrating the superior in vitro and in vivo biological activity of CAR-Tregs engineered using HydroporeTM relative to those engineered using traditional methods. Pending the successful completion of these objectives, CAR-Tregs will be engineered using Treg cells isolated from T1D patients and demonstrate clinical- and commercial-scale processing and enrichment of sufficient CAR-Tregs cells for human trials.