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

使用去核间充质干细胞治疗肺部疾病的治疗平台0/01/2021

基本信息

批准号：
10257613
负责人：
Remo Moomiaie
金额：
$ 45.5万
依托单位：
CYTONUS THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-16 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10257613
关键词：
Acute Lung Injury Address Adult Respiratory Distress Syndrome Biodistribution Biological Bioluminescence Blood Vessels CXCR4 Receptors CXCR4 gene Cell Adhesion Molecules Cell Nucleus Cell Therapy Cells Clinical Clustered Regularly Interspaced Short Palindromic Repeats DNA Data Disease Doxorubicin Drug Delivery Systems Drug Kinetics Drug Transport Endothelium Engineering Environment Extracellular Matrix Proteins Extravasation Face Genetic Engineering Genetic Transcription Golgi Apparatus Grant Granulocyte-Macrophage Colony-Stimulating Factor Home Homing Immune response Immunofluorescence Microscopy Immunomodulators In Vitro Inflammation Interleukin-10 Interleukin-12 Interleukin-15 Intravenous Invaded Kinetics Legal patent Licensing Longevity Lung Lung diseases Mediating Medical center Mesenchymal Mesenchymal Stem Cells Mitochondria Modeling Nanotubes Organ Organelles P-selectin ligand protein Patients Peptides Pharmaceutical Preparations Phase Production Proliferating Protein Secretion Proteins RNA Resolution Respiratory System Risk Route Safety Site Small Interfering RNA Structure of parenchyma of lung System Testing Therapeutic Therapeutic Agents Vesicle Virus Work antibody engineering cell behavior cell type clinically relevant cytokine exosome extracellular vesicles fMet-Leu-Phe receptor gene therapy improved in vivo lung injury migration mouse model nanoparticle novel novel therapeutics nuclear transfer patient safety preclinical study prevent prototype small hairpin RNA stem stem cells synthetic drug targeted delivery therapeutic protein tumorigenesis uptake zinc finger nuclease

项目摘要

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.

对于可以静脉注射（IV）施用的基于细胞的疗法，有效地需要进行基于细胞的疗法，并有效地需要在维持患者安全的同时，向呼吸系统进行治疗。 Cytonus Therapeutics和加州大学圣地亚哥分校的医疗中心正在共同开发含核的间充质干细胞，并有可能提供多种生物制剂治疗呼吸道疾病，包括急性呼吸窘迫综合征（ARDS）。我们的治疗递送的新型平台是与基因工程师间充质干细胞（MSC）一起使用的平台炎症归巢蛋白，然后轻轻去除细胞核，从而提供高度独特，可行和具有巨大肺归巢潜力的安全细胞治疗（cargocytestm）。偶像有能力具有多个肺靶向部分和广泛的生物有效载荷的遗传工程师碳细胞，同时保持临床相关的安全性。我们的肺定位策略是建立在关键潜力上的通过静脉内路线（i.v.），对肺部进行活跃的靶向递送。成核 MSC首先将通过已建立的趋化受体CXCR4/CCR2进行广泛设计，并发炎内皮粘附分子PSGL-1，然后在静脉内进行摘除。行政。概念证明然后将进行临床前研究，以确定是否用肺营养进行了碳细胞分子在ARDS的临床相关鼠模型中在肺部发炎。因此，AIM 1研究将确定用ccxcr4/ccr2和psgl-1家用碳细胞为发炎的肺组织制造并瞄准2 研究将确定碳细胞是否退出脉管系统并进入发炎/受损的肺实质。如果碳细胞在发炎的肺组织并退出脉管系统中，它可以提供一种有效的方法来治疗广泛的呼吸道疾病。