This disclosure describes, generally, a modified form of CD16, genetically-modified cells that express the modified CD16, and methods that involve the genetically-modified cells. The modified form of CD16 can exhibit increased anti-tumor and/or anti-viral activity due, at least in part, to reduced susceptibility to ADAM17-mediated shedding upon NK cell stimulation.

Provided herein are methods of producing heparin and heparan sulfate from modified cells, such as modified MST cells, and compositions comprising heparin and heparan sulfate isolated from modified cells.

The disclosure provides methods for the long-term expansion of granulocyte-macrophage progenitors, the granulocyte-macrophage progenitors generated therefrom, and uses of the granulocyte-macrophage progenitors thereof.

The present invention relates to compositions and methods that provide novel anti-tumor therapies in cancer. In one aspect, the present invention features a hybrid neutrophil in a non-naturally occurring container, wherein the hybrid neutrophil expresses at least one neutrophil associated molecule selected from the group consisting of: Arg1, MPO, CD66b, and CD15, and at least one antigen-presenting cell (APC) associated molecule selected from the group consisting of: CD14, HLA-DR, CD32, CD64, and CD89. In another aspect, the present invention features methods of generating a hybrid neutrophil. In still another aspect, the present invention features methods of inhibiting tumor growth in a subject, treating a tumor in a subject, and increasing efficacy of an antibody against a tumor in a subject. The methods comprise (a) administering to the subject an effective amount of an anti-tumor antibody and (b) administering to or generating in the subject an effective amount of a hybrid neutrophil.

In one aspect, a method of treating a subject having or at risk of having graft-versus-host disease (GvHD) generally includes administering to the subject a plurality of myeloid-derived suppressor cells (MDSCs) effective to ameliorate at least one symptom or clinical sign of graft-versus-host disease compared to a suitable control subject. In another aspect, a method of treating a tumor in a subject generally includes administering to the subject an anti-tumor therapy and co-administering to the subject an inflammasome inciting agent in an amount effective to increase inflammasome activation of MDSCs sufficiently to reduce suppressor function of the MDSCs.

An artificial immune cell emulating certain properties of the granulocytes is disclosed as a construct or aggregate of several constituent particles that possess the properties of catalysis therefore producing free radicals and reactive species of oxygen, nitrogen, halogens and the like in the classical Fenton and Fenton-like reactions with produced free radicals serving as signaling molecules and, in higher concentrations, as toxic factors for microorganisms, cancerous cells, abnormal tissue and other biological targets, emulating the production of free radicals by natural immune cells. Motility of the artificial immune cell is facilitated by magnetotactic and other means, as some or all of the constituent particles possess magnetic, especially superparamagnetic properties which may be provided by the same catalytic components since said particles such as those containing compounds such as magnetite, maghemite, and substituted ferrites are capable of catalyzing Fenton-type reactions. Constituent particles of the artificial immune cell may be coated with agents facilitating specific targeting and binding such as antibodies to target antigenes, they may also interact with the intrinsically present natural immune cells by presenting antigens or antibody fragments. Other constituent particles of the artificial immune cell may be coated with lipid bilayers with sequestered biologically active molecules that are released as the lipid bilayer is destroyed by free radicals or they may contain cavities or internal spaces filled with biologically active molecules and capped or sealed with easily oxidizable materials facilitating the release of such molecules in the presence of aggressive oxidants such, thus emulating the property of granulocytes known as degranulation. A variety of the constituent particle may be a capped hollow cylinder with the internal walls presenting with excess of negative electric charges and filled with compacted nucleic acid-protein mixtures whereas upon destruction of the caps the repulsive electric force pushes out the nucleic acid-protein mixture emulating the property of neutrophils known as formation of neutrophil extracellular traps. Modification, modulation and termination of the activity of the artificial immune cell is accomplished by removal by magnetotactic locomotion, disruption with energetic waves, extinguishing of Fenton and Fenton-type reactions by introduction of reaction termination conditions such as excess of antioxidants. Additional refinements are disclosed with specific chemical and physical alterations of the constituent particles or the complete artificial immune cell.

A method of obtaining a population of cells enriched in human polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs) comprises isolating from a cell suspension those cells which express LOX-1 to provide a population of cells enriched with PMN-MDSCs. A method of monitoring the population of LOX-1+ cells in a cell-containing biological sample is useful for determining the efficacy of treatment or the metastasis or increasing progression of cancer. Other cell isolation and diagnostic methods are also described.

The invention relates to polypeptides and chimeric antigen receptors (CARs) comprising an intracellular domain of a Fc alpha Receptor (FcR), a transmembrane domain of a FcR, and a ligand-binding domain, to cells comprising and expressing such polypeptides and CARs and to uses thereof.

Methods and systems for removing leukocytes from a biological fluid are disclosed. The methods and systems include a chamber containing particles to which the leukocytes adhere. Such particles may carry an electrostatic charge. In one example, the particles comprise a polymer having an acid number of 5 or greater.

The present invention allows a TET1 protein to be more stably expressed in human pluripotent stem cells than in the past by, inter alia, substituting the second amino acid from the amino terminal of a TET1 protein with a different amino acid. Furthermore upon differentiation of said pluripotent stem cells, it is possible to quickly eliminate the expression of, inter alia, NANOG, which is an inhibitor of differentiation and promote the expression of factors related to differentiation by introducing a variant TET1 protein to a pluripotent stem cell. The present invention provides a method for manufacturing pluripotent stem cells with increased differentiation potential, and a substance that is useful to said method.