Therapeutic platform to treat disease lung using enucleated mesenchymal stem cells0/01/2021

迫切需要基于细胞的治疗剂，其可以静脉内（IV）施用，并且有效地将细胞内的细胞聚集到细胞内。 并将治疗剂输送到呼吸系统，同时保持患者安全。Cytonus治疗和 加州大学圣地亚哥分校的医学中心正在共同开发去核间充质干细胞， 广泛的生物制剂治疗呼吸系统疾病，包括急性呼吸窘迫综合征（ARDS）。我们 用于治疗递送的新平台是遗传工程化间充质干细胞（MSC）， 炎症归巢蛋白，然后轻轻地去除细胞核，从而提供一个高度独特的，可行的， 安全的细胞治疗剂（CargocytesTM），具有显著的肺归巢潜力。眼球摘除赠款让人 用多个肺靶向部分和广泛的生物有效载荷对Cargocyte进行基因工程改造， 同时保持临床相关的安全性。我们的肺部靶向策略建立在以下关键潜力之上： Cargocyte治疗剂通过静脉内途径（i. v.）向肺部进行活性靶向递送。有核 MSC将首先用已建立的趋化因子受体CXCR 4/CCR 2进行广泛工程化， 内皮粘附分子PSGL-1，然后在静脉内给药前去核。概念验证 然后将进行临床前研究以确定是否用肺营养因子工程化Cargocytes。 在临床相关的ARDS小鼠模型中，因此，目标1研究将 确定用CCXCR 4/CCR 2和PSGL-1工程化的Cargocytes是否归巢于发炎的肺组织和Aim 2 研究将确定是否Cargocyte离开脉管系统并移动到发炎/受损的肺实质中。如果 当癌细胞回到发炎的肺组织并离开脉管系统时，它可以提供一种有效的治疗方法。 各种呼吸道疾病。

There is critical need for cell-based therapeutics that can be administered intravenously (IV), and effectively home to and deliver therapeutics to the respiratory system, while maintaining patient safety. Cytonus Therapeutics and UC San Diego's Medical Center are co-developing enucleated mesenchymal stem cells with potential to deliver a wide range of biologics to treat respiratory diseases including acute respiratory distress syndrome (ARDS). Our novel platform for therapeutic delivery is to genetically engineer mesenchymal stem cells (MSCs) with inflammation homing proteins and then gently remove the nucleus, thereby providing a highly unique, viable, and safe cell therapeutic (CargocytesTM) with substantial lung homing potential. Enucleation grants the ability to genetically engineer Cargocytes with multiple lung targeting moieties and a wide range of biological payloads, while maintaining a clinically relevant safety profile. Our lung targeting strategy is built on the key potential of Cargocyte therapeutics to perform active-targeted delivery to the lungs via an intravenous route (i.v.). Nucleated MSCs will first be extensively engineered with established chemoattractant receptors CXCR4/CCR2 and inflamed endothelial adhesion molecule PSGL-1 and then enucleated prior to i.v. administration. Proof-of-concept preclinical studies will then be performed to determine whether Cargocytes engineered with lung trophic molecules home to inflamed lungs in a clinically relevant murine model of ARDS. Therefore, Aim 1 studies will determine if Cargocytes engineered with CCXCR4/CCR2 and PSGL-1 home to inflamed lung tissues and Aim 2 studies will determine if Cargocytes exit the vasculature and move into the inflamed/damaged lung parenchyma. If Cargocytes home to inflamed lung tissues and exit the vasculature, it could provide an effective means to treat a wide range of respiratory diseases.