A recombinant nucleic acid expression construct including a first nucleic acid sequence region encoding a chimeric antigen receptor (CAR), a second nucleic acid sequence region encoding a checkpoint inhibitory molecule, and a third nucleic acid sequence region encoding an immune stimulatory cytokine. A recombinant nucleic acid expression construct encoding the CAR specifically recognizes CD44v6, and includes a PD1 checkpoint inhibitory molecule, and an immune stimulating cytokine. Further aspects relate to genetically modified cells, including a recombinant nucleic acid expression construct encoding the CAR, wherein the cells are preferably immune cells, more preferably NK cells or cytotoxic T lymphocytes or T helper cells. Medical use of the cells may be in the treatment of a medical disorder associated with the presence of pathogenic cells expressing CD44v6, preferably cancer cells, more preferably cancer stem cells of solid or liquid malignancies.

The present disclosure relates to a stage-specific process for manufacturing a population of neutrophils, such as chimeric antigen receptor-expressing (CAR-expressing) neutrophils (e.g., T cells and natural killer (NK) cells), from human pluripotent stem cells (hPSCs) using defined media and related compositions, kits, and methods of use (e.g., targeted cancer immunotherapy). Stage-specific processes for generating neutrophils and chimeric antigen receptor (CAR) neutrophils from human pluripotent stem cells (hPSCs) using chemically defined, feeder-free platforms and stage-specific morphogens; cell lines; pharmaceutical compositions; a method of treating cancer; and a kit are within the scopes of this disclosure.

This disclosure provides nano-scale Artificial Antigen Presenting Cells (aAPC), which deliver stimulatory signals to lymphocytes, including T-helper lymphocytes, for use as a powerful tool for immunotherapy.

The present invention relates to methods for producing immuno-stimulatory antigen-presenting cells. The present invention further relates to the use of such cells for treating patients suffering from hyper-proliferative disease such as cancer.

The use of luteinizing hormone receptor (LHR) binding agents and luteinizing hormone (LH) agonists to enrich for primitive hematopoietic stem cell (pHSC) populations, to target pHSC for ablation, and/or to expand pHSC populations are described. The methods can be used to prepare therapeutic hematopoietic stem cell (HSC) populations, to prepare patients for therapeutic HSC transplants, and/or to treat malignancies, such as those associated with hyperproliferative HSC.

Provided herein are, inter alia, compositions comprising ex vivo expanded ILC1 cells, methods of preparing the compositions, and methods useful for treating cancer and leukemia.

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.

The inventors explored in an allogeneic situation the regulatory potential of Mucosal-Associated Invariant T cells (MAIT cells), a population of unconventional T cells that exhibit potent antibacterial activity, expressing a semi-invariant TCR which recognizes vitamin B2 derivatives of microbial origin presented by the MR1 molecule. In particular, the inventors used i) an allogenic reaction model in vitro (mixed lymphocyte reaction, MLR) and ii) murine model of xenogeneic aGvHD They first verified that human MAIT cells do not proliferate in response to allogeneic stimulation in vitro (MLR) or in vivo (immunodeficient mice) alone but require for their expansion both an inflammatory environment and TCR ligation by its ligand. In contrast, MAIT cells are able to inhibit the proliferation of allospecific LT in vitro in a dose-dependent manner. Furthermore, the adoptive transfer of MAIT cells in a mouse model of xeno-GVHD resulted in a delay in early or late GvHD development. Altogether, these data describe a new regulatory function of MAIT cells in an allogeneic context, allowing us to consider their use in cell therapy to limit GvHD.

This invention provides a method for depleting a subject's hematopoietic stem cells comprising administering to the subject an effective amount of a radiolabeled anti-CD45 antibody, such as .sup.131I-BC8 or .sup.225Ac-BC8. This invention also provides a method for treating a subject afflicted with a non-cancerous disorder treatable via genetically edited cell therapy comprising (i) administering to the subject an amount of a radiolabeled anti-CD45 antibody effective to deplete the subject's hematopoietic stem cells, and (ii) after a suitable time period, performing the therapy on the subject to treat the subject's disorder. Finally, this invention provides articles of manufacture for performing the subject methods.

The novel synergistic combination of immune checkpoint blockade and hematopoietic stem cell transplantation and/or hematopoietic stem cell mobilization yield synergistic effects in disease therapy.