Healthy functional platelets are mass produced. A method for producing platelets, comprising: (1) a culture step of culturing megakaryocytes in a platelet producing medium in the presence of mechanical stress and platelet production promoting factors including MIF, NRDc, IGFBP2, TSP-1, PAI-1, and CCL5, and (2) a harvest step of harvesting the platelets obtained by the culture step; wherein the culture step comprises: (a) a step of promoting a release of the platelet production promoting factors from megakaryocytes by mechanical stress; and/or (b) a step of externally adding platelet production promoting factors including MIF, NRDc, and IGFBP2.

The present invention relates to a fusion protein comprising at least two cytokines, of which at least one is a modified cytokine with a strongly reduced binding affinity to its receptor, or to one of its receptors. Preferably, both cytokines are connected by a linker, preferably a GGS linker. The invention relates further to said fusion protein for use in treatment of diseases.

The invention provides compositions and methods for targeting CCR10 and/or the CCR10/ligand axis to modulate the immune response in a subject.

Checkpoint receptors and their cognate ligands are frequently targeted in autoimmune disorders by B and T cells, wherein these adaptive immune responses are likely to significantly contribute to the underlying immunopathology. A novel technology for the clonal elimination of autoreactive B cells that targets checkpoint receptors and their ligands is described herein. One embodiment of this technology is a checkpoint receptor or ligand extracellular domain molecular chimera with an effector domain, which is capable of inducing B cell apoptosis, necrosis, and/or tolerization/anergization: herein, this technology is referred as PantIds (polyclonal anti-idiotypics). In other embodiments, this technology also includes effector molecular chimeras with immunoregulatory cytokines. Novel apoptotic effectors are also described. Methods for the identification of checkpoint receptor/ligand autoreactive B cell responses, construction of PantIds, and their in vitro and in vivo application are also described.

The present disclosure provides a oncolytic adenovirus with selectivity for cancer cells, wherein the adenovirus comprises a transgene under the control of a promoter endogenous to the virus, wherein the transgene comprises a DNA sequence encoding a membrane anchored anti-CD3 antibody or a binding fragment thereof, compositions comprising same, methods of generating the viruses, and use of the viruses and compositions in treatment, particularly in the treatment of cancer.

A fusion molecule is provided that includes one or more inhibitory nucleic acids, a targeting polypeptide, and a nucleic acid binding moiety. The targeting polypeptide and the nucleic acid binding moiety include specific the amino acid sequences. A fusion molecule is also provided that includes one or more inhibitory nucleic acids, a targeting polypeptide, and a nucleic acid binding moiety adapted to bind a double-stranded RNA or to a small hairpin RNA. The targeting polypeptide being IL6 or IL21 or a fragment thereof.

A fusion molecule is provided that includes one or more inhibitory nucleic acids, a targeting polypeptide, and a nucleic acid binding moiety. The targeting polypeptide and the nucleic acid binding moiety include specific the amino acid sequences. A fusion molecule is also provided that includes one or more inhibitory nucleic acids, a targeting polypeptide, and a nucleic acid binding moiety adapted to bind a double-stranded RNA or to a small hairpin RNA. The targeting polypeptide being CCL27 or CCL11 or a fragment thereof.

The invention provides compositions and methods useful for mobilizing populations of hematopoietic stem and progenitor cells within a donor, as well as for determining whether samples of mobilized cells are suitable for release for ex vivo expansion and/or therapeutic use. In accordance with the compositions and methods described herein, mobilized hematopoietic stem and progenitor cells can be withdrawn from a donor and administered to a patient for the treatment of various stem cell disorders, including hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others. In certain embodiments, the compositions and methods described herein lead to the mobilization of a population of CD34.sup.dim cells that have immunosuppressive effects and that can reduce the incidence of graft vs. host disease.

Healthy functional platelets are mass produced. A method for producing platelets, comprising: (1) a culture step of culturing megakaryocytes in a platelet producing medium in the presence of mechanical stress and platelet production promoting factors including MIF, NRDc, IGFBP2, TSP-1, PAI-1, and CCL5, and (2) a harvest step of harvesting the platelets obtained by the culture step; wherein the culture step comprises: (a) a step of promoting a release of the platelet production promoting factors from megakaryocytes by mechanical stress; and/or (b) a step of externally adding platelet production promoting factors including MIF, NRDc, and IGFBP2.

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.