公开(公告)号：US20240301019A1

公开(公告)日：2024-09-12

申请号：US18262648

申请日：2022-02-14

申请人： ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIVERSITY OF ARIZONA

发明人： Young-Wook WON ,  Seungmin HAN ,  David A. BULL

IPC分类号： C07K14/47 ,  A61K35/17 ,  A61K38/00 ,  A61P35/00 ,  C12N5/0783

CPC分类号： C07K14/4705 ,  A61K35/17 ,  A61P35/00 ,  C12N5/0646 ,  A61K38/00 ,  C07K2319/09 ,  C07K2319/10 ,  C07K2319/21

摘要： Described herein is a recombinant Eomes protein that restores the cytotoxic activity of exhausted immune cells. This protein comprises, a nuclear localization sequence (NLS), the transcription factor associated domain of Eomesodermin (Eomes), and a protein-transduction domain (PTD). The NLS-Eomes-PTD polypeptide spontaneously internalizes into NK cells and travels to the nucleus to control the transcription of its down-stream signaling pathways. Introduction of the NLS-Eomes-PTD polypeptide into ExNK cells (i) decreases the expression of an inhibitory antigen on ExNK cells; (ii) increases cytolytic activity: (iii) enhances cytokine secretion; (iv) improves proliferation; and (v) inhibits tumor growth.

公开(公告)号：US20230302135A1

公开(公告)日：2023-09-28

申请号：US18042263

申请日：2021-08-25

申请人： ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIVERSITY OF ARIZONA

发明人： Young-Wook WON ,  Byeong-Hyun CHA ,  David A. BULL

IPC分类号： A61K39/00 ,  C07K14/715 ,  C07K14/71 ,  C07K14/705 ,  C12N5/077

CPC分类号： A61K39/4637 ,  C07K14/7158 ,  C07K14/71 ,  C07K14/70517 ,  C12N5/0657 ,  C07K2319/03 ,  C12N2501/21 ,  C12N2501/06 ,  C12N2506/1353

摘要： Described herein are mesenchymal stem cells (MCS) expressing hybrid allosteric receptors (HAR) that are responsive to stromal cell-derived factor 1 alpha (SDF-1α) secreted from acutely infarcted myocardium. Binding of SDF-1α to CXCR4 activates the co-stimulatory signals, bone morphogenetic protein 2 type II receptor (BMP2R2) and BMP type I receptor (ALK3), in order to accelerate the differentiation into cardiomyocytes. HAR-MSC CXCR4 differentiates into cardiomyocytes through Smad1/5 phosphorylation induced by the BMP2 signaling. In acute myocardial infarction (AMI) models, HAR-MSC CXCR4 treatment leads to the functional improvements by facilitated differentiation and increased cytokine secretion. HAR-MSC CXCR4 cells can be used for the treatment of AMI.