The present invention relates to a receptor-binding domain of an IgE-dependent histamine releasing factor (HRF), and a use thereof, and more specifically, ascertains, as an HRF structural region, and a FL domain and an H2 domain which bind to a receptor of HRF existing in a cell membrane, ascertains the C-terminus domain of the HRF, and ascertains that a material binding thereto inhibits IL-8 secretion, thereby determining that the FL and H2 domains and the C-terminus domain can be utilized in: the development of a therapeutic agent for treatment and prevention of HRF-related disease including allergic diseases such as asthma, rhinitis, atopic dermatitis, and anaphylaxis; inflammatory diseases such as rheumatoid arthritis; and malaria, and a method for screening for the HRF-related diseases.

The present invention relates to a receptor-binding domain of an IgE-dependent histamine releasing factor (HRF), and a use thereof, and more specifically, ascertains, as an HRF structural region, and a FL domain and an H2 domain which bind to a receptor of HRF existing in a cell membrane, ascertains the C-terminus domain of the HRF, and ascertains that a material binding thereto inhibits IL-8 secretion, thereby determining that the FL and H2 domains and the C-terminus domain can be utilized in: the development of a therapeutic agent for treatment and prevention of HRF-related disease including allergic diseases such as asthma, rhinitis, atopic dermatitis, and anaphylaxis; inflammatory diseases such as rheumatoid arthritis; and malaria, and a method for screening for the HRF-related diseases.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The present invention provides for the intratumoral delivery of at least one immunostimulatory cytokine in combination with at least one checkpoint inhibitor. In particular, it provides delivery of a plasmid encoding the immunostimulatory cytokine using intratumoral electroporation. The checkpoint inhibitor may be administered systemically or encoded on a plasmid and delivered using intratumoral electroporation. The checkpoint inhibitor may be delivered contemporaneously with or after treatment with the immunomodulatory cytokine.

The present invention provides for the intratumoral delivery of at least one immunostimulatory cytokine in combination with at least one checkpoint inhibitor. In particular, it provides delivery of a plasmid encoding the immunostimulatory cytokine using intratumoral electroporation. The checkpoint inhibitor may be administered systemically or encoded on a plasmid and delivered using intratumoral electroporation. The checkpoint inhibitor may be delivered contemporaneously with or after treatment with the immunomodulatory cytokine.

Materials and methods for treating a patient with a hemoglobinopathy, both ex vivo and in vivo, and materials and methods for creating permanent changes to the genome that can result in at least one deletion, insertion, modulation, or inactivation of a transcriptional control sequence of a BCL11A gene in a cell by genome editing.

Provided are methods for the treatment of SCLC patients by administering therapeutic amounts of lurbinectedin by intravenous infusion. Also provided are methods of treating cancer by administering lurbinectedin in combination with other anticancer drugs, in particular topoisomerase inhibitors. The invention further relates to the administration of lurbinectedin in combination with anti-emetic agents for effective control of symptoms related to nausea and vomiting, reduced lurbinectedin dosages to achieve a safer administration and an increase in the number of treatment cycles. Stable lyophilized formulations of lurbinectedin are also provided.

The present disclosure provides methods comprising administering to the individual an effective amount of an agent that decreases or inhibits TIGIT expression and/or activity and an anti-cancer agent and/or an anti-cancer therapy. Further provided are kits comprising an anti-cancer agent, an agent that decreases or inhibits TIGIT expression and/or activity, or both, as well as instructions for use thereof.

The described invention identifies endothelial cells within the perivascular niche as a crucial component in driving bone marrow (BM) inflammation and HSC dysfunction. We demonstrate that crosstalk between ERK-MAPK and NF-κB signaling pathways within the endothelium plays a key role in modulating the outcomes of chronic inflammation. Sustained activation of the MAPK pathway selectively within the endothelium of adult mice leads to inflammation-induced HSC dysfunction including loss of engraftment ability and a myeloid-biased output. HSC defects caused by endothelial MAPK activation are completely resolved upon simultaneous inhibition of endothelial NF-κB signaling. The described invention identifies Stem Cell Growth Factor alpha (SCGF) as a niche-derived factor that suppresses BM inflammation and enhances hematopoietic recovery following myelosuppressive injury.

The described invention identifies endothelial cells within the perivascular niche as a crucial component in driving bone marrow (BM) inflammation and HSC dysfunction. We demonstrate that crosstalk between ERK-MAPK and NF-κB signaling pathways within the endothelium plays a key role in modulating the outcomes of chronic inflammation. Sustained activation of the MAPK pathway selectively within the endothelium of adult mice leads to inflammation-induced HSC dysfunction including loss of engraftment ability and a myeloid-biased output. HSC defects caused by endothelial MAPK activation are completely resolved upon simultaneous inhibition of endothelial NF-κB signaling. The described invention identifies Stem Cell Growth Factor alpha (SCGF) as a niche-derived factor that suppresses BM inflammation and enhances hematopoietic recovery following myelosuppressive injury.