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

• 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
• 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

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.

目前迫切需要能够静脉注射（IV）并在家中有效使用的基于细胞的治疗方法