Use of a composition comprising a combination of a NAD+ precursor, preferably Nicotinamide Riboside and Vitamin B12 for increasing stem cell function in a population of haematopoietic stem and/or progenitor cells (HSPCs).

The present invention relates to a method for inducing differentiation of bone marrow cells into myeloid-derived suppressor cells (MDSCs) by treating the bone marrow cells with a toll-like receptor agonist (TLR agonist) or type I interferon, or for inducing dendritic cells from the MDSCs.

Among the various aspects of the present disclosure is the provision of compositions and methods of making modified chimeric antigen receptor dendritic cells (CAR-DCs) and methods of use thereof. CAR-DCs can be used for the treatment of tumors and cancers, particularly solid tumors (as well as liquid tumors, blood cancer, and metastatic cancer).

Embodiments of the instant disclosure relate to novel compositions, methods and systems for generating ILC cells. In certain embodiments, the present disclosure provides for a composition including a hematopoietic progenitor cell expressing CD48 and at least one of a CD48 ligand, a CD48 agonist or a CD48 antagonist in order to induce production of ILC2 or ILC3 (for example, NCR.sup.+ ILC3 and LTi-ILC3) cell populations. In other certain embodiments, the present disclosure provides methods of treating one or more health condition or immune-mediated condition in a subject by administering an effective amount of a composition of ILC2 or ILC3 cells generated using methods disclosed herein.

The present invention relates to an in vitro culture of haematopoietic cells, wherein said haematopoietic cells differentiate to form granulocytes characterised by the ability to kill cancer cells. The invention also relates to said granulocytes, methods for identifying said haematopoietic cells and granulocytes, compositions and kits comprising the same, as well as uses of the same for treating cancer.

Provided herein are cells engineered to have improved protection against natural killer cell killing. The cells are engineered to comprise an insertion of a polynucleotide encoding SERPINB9. Also provided herein are methods of making the engineered cells and therapeutic uses of the engineered cells. The engineered cells can also comprise at least one genetic modification within or near at least one gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or component or transcriptional regulator of the MHC-I or MHC-II complex, at least one genetic modification that increases the expression of at least one polynucleotide that encodes a tolerogenic factor, and optionally at least one genetic modification that increases or decreases the expression of at least one gene that encodes a survival factor. The engineered cells can be stem cells and the engineered stem cells can be differentiated into various lineages having protection against NK cell killing.

The present disclosure relates to compositions, nucleic acid constructs, methods and kits thereof for cell induction or reprogramming cells to the dendritic cell state or antigen presenting cell state, based, in part, on the surprisingly effect described herein of novel use and combinations of transcription factors that permit induction or reprogramming of differentiated or undifferentiated cells into dendritic cells or antigen presenting cells. Such compositions, nucleic acid constructs, methods and kits can be used for inducing dendritic cells in vitro, ex vivo, or in vivo, and these induced dendritic cells or antigen presenting cells can be used for immunotherapy applications.

The disclosure features methods and compositions for differentiating stem cells into hematopoietic stem and progenitor cells (HSPC) and/or Natural Killer (NK) cells. The methods and compositions described herein are used to differentiate stem or progenitor cells having at least one gene-edit that is maintained in the differentiated cell. Also provided are differentiated cells produced using the methods and compositions described herein for therapeutic applications.

Provided herein are methods of producing natural killer cells using a two-step expansion and differentiation method. Also provided herein are methods of suppressing tumor cell proliferation, of treating individuals having cancer or a viral infection, comprising administering the NK cells produced by the method to an individual having the cancer or viral infection.

The present invention relates to methods, kits and compositions for expansion of embryonic hematopoietic stem cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGFβ pathway. Also provided herein are methods for expanding embryonic hematopoietic stem cells using kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGFβ pathway. The embryonic hematopoietic stem cells expanded using the disclosed kits, compositions and methods include cells derived from an embryo (e.g., aorta-gonad-mesonephros region of the embryo), embryonic stem cells, induced pluripotent stem cells, or reprogrammed cells of other types. The present invention also relates to administering the embryonic hematopoietic stem cells expanded using a combination of a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGFβ pathway to a patient for short-term and/or long-term in vivo repopulation benefits.