Provided herein are methods of producing natural killer (NK) cells and/or ILC3 cells using a three-stage expansion and differentiation method with media comprising stem cell mobilizing factors. Also provided herein are methods of suppressing tumor cell proliferation using the NK cells and/or ILC3 cells and the NK cell and/or ILC3 cell populations produced by the three-stage methods described herein, as well as methods of treating individuals having cancer or a viral infection, comprising administering the NK cells and/or ILC3 cells and the NK cell and/or ILC3 cell populations produced by the three-stage methods described herein to an individual having the cancer or viral infection.

ILC2 cells play a role in the pathogenesis of graft versus host disease (GvHD) and idiopathic pneumonia syndrome (IPS), both conditions associated with allogeneic stem cell transplantation. Infusion of IL-33 activated ILC2 cells into patients with ongoing GvHD or IPS, or prior to onset of GvHD or IPS in susceptible patients, substantially ameliorates the disease and improves survival.

Provided herein are methods and compositions related to polyomavirus epitopes useful in the treatment of cancer or a polyomavirus infection.

The present invention provides gene edited modified immune cells suitable for adoptive T cell therapy comprising a nucleic acid capable of downregulating CD3δ, CD3ε, CD3γ, B2M, CIITA, TAP1, TAP2, TAPBP, NLRC5, HLA-DM, RFX5, RFXANK, RFXAP, and invariant chain; and further comprising an exogenous nucleic acid encoding a chimeric antigen receptor (CAR), an engineered T cell receptor (TCR), a Killer cell immunoglobulin-like receptor (KIR), dominant negative receptor and/or a switch receptor. Also provided are compositions and methods for generating the modified immune cell, and methods of using the modified immune cells for adoptive therapy and treating a disease or condition.

Innate lymphoid cells (ILCs) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCP). Still, how ILCP relate to mature tissue-resident ILCs remains unclear. ILCP that are present in the blood and all tested lymphoid and non-lymphoid human tissues were identified. Human ILCP fail to express the signature transcription factors (TF) and cytokine outputs of mature NK cells and ILCs but are epigenetically poised to do so. Human ILCP robustly generate all ILC subsets in vitro and in vivo. While human ILCP express RAR related orphan receptor C (RORC), circulating ILCP can be found in RORC-deficient patients that retain potential for EOMES.sup.+ NK cells, T-BET.sup.+ ILC1, GATA-3.sup.+ ILC2 and for IL-22.sup.+ but not for IL-17A.sup.+ ILC3. A model of tissue ILC differentiation (‘ILC-poiesis’) is proposed whereby diverse ILC subsets are generated in situ from ILCP in response to environmental stressors, inflammation and infection.

Provided herein are methods of producing engineered T cell compositions enriched for CD57 negative and/or CD27 positive T cells, such as from a plurality of donors. In some embodiments, the T cells are engineered with a recombinant receptor, such as a chimeric antigen receptor (CAR). Also provided herein are engineered T cell compositions containing T cells enriched for CD57 negative and/or CD27 positive T cells derived from a plurality of different donors, including compositions in which the T cells are engineered with or express a recombinant receptor (e.g. CAR). Also provided are methods of using the engineered T cell compositions in adoptive therapy, including in connection for cancer immunotherapy, such as for allogeneic therapies or for administration to one or more subjects in which the T cells are not derived from the subject(s) to whom the compositions are administered.

The disclosure provides methods of treating coronavirus infections (e.g., COVID-19) by administering hematopoietic stem cells, with or without an immune checkpoint inhibitor (e.g., PD-1 antagonist). The disclosure also provides methods of treating coronavirus infections (e.g., COVID-19) by adoptive cell transfer of polyclonal T cells and coronavirus-specific T cells (e.g., SARS-CoV-2-specific T cells).

There is described herein a method of enriching a population of stem cells for hematopoietic progenitors. The method comprises inducing hematopoietic differentiation in a population of human embryonic stem cells or human induced pluripotent stem cells; sorting the population based on expression of CD43 and at least one of CD34, CD31 and CD144; and selecting a fraction that is at least one of CD34+CD43−, CD31+CD43− and CD144+CD43−. Also provided are populations of hematopoietic progenitors obtained by the methods described herein.

The present disclosure provides methods of preparing immune cells, e.g., T cells and/or NK cells, comprising contacting the cells with programmable cell-signaling scaffolds in a medium comprising at least about 5 mM potassium ion. In some aspects, the methods disclosed herein increase the number of less-differentiated cells in the population of cells. In some aspects, the cultured cells are engineered, e.g., to comprise a chimeric antigen receptor (CAR) or an engineered T cell receptor (TCR). In some aspects, the cells are administered to a subject in need thereof.

Provided are an artificial multi-antigen fusion protein and a preparation method thereof. The fusion protein can effectively stimulate CD8+T and CD4+ T cell immunities, and can be applied to immunodiagnostics or serve as a prophylactic or therapeutic vaccine.