This disclosure relates to methods for producing immune cells with enhanced function. More specifically, disclosed herein is a method for enhancing the function of an immune cell comprising modifying an immune cell to inhibit the function of at least one gene selected from the group consisting of RC3H1, RC3H2, A2AR, FAS, TGFBR1, and TGFBR2. Also disclosed herein is a method comprising modifying a stem or progenitor cell capable of differentiating into an immune cell to inhibit the function of at least one gene selected from the group consisting of RC3H1, RC3H2, A2AR, FAS, TGFBR1, and TGFBR2. Also disclosed herein are immune cells or stem cells made by the present methods, as well as the use of immune cells in therapeutic treatment.

Chimeric antigen receptors containing CD123 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

The present invention relates to, inter alia, an engineered cell (e.g., iPSC, IPS-derived NK, or NK cell) comprising a disrupted B2M gene and an inserted polynucleotide encoding one or more of SERPINB9, a fusion of IL15 and IL15Rα, and/or HLA-E. The engineered cell can further comprise a disrupted CIITA gene and an inserted polynucleotide encoding a CAR, wherein the CAR can be an anti-BCMA CAR or an anti-CD30 CAR. The engineered cell may further comprise a disrupted ADAM17 gene, a disrupted FAS gene, a disrupted CISH gene, and/or a disrupted REGNASE-1 gene. Methods for producing the engineered cells are also provided, and therapeutic uses of the engineered cells are also described. Guide RNA sequences targeting described target sequences are also described.

The invention relates to a method for activating and expanding NKT-like cells in vitro. The method according to the present invention utilizes nucleated somatic cells derived from allogeneic or heterologous subjects to activate and proliferate NKT-like cells of a subject in vitro, and can increase the overall number of the NKT-like cells, the expression of activation markers and the number of killing effector molecules.

The invention relates to a system, comprising: a) a sample processing unit, comprising an input port and an output port coupled to a rotating container having at least one sample chamber, the sample processing unit configured provide a first processing step to a sample or to rotate the container so as to apply a centrifugal force to a sample deposited in the chamber and separate at least a first component and a second component of the deposited sample; and b) a sample separation unit coupled to the output port of the sample processing unit, the cell separation unit comprising separation column holder (42), a pump (64) and a plurality of valves (1-11) configured to at least partially control fluid flow through a fluid circuitry and a separation column (40) positioned in the holder, the separation column configured to separate labeled and unlabeled components of sample flowed through the column.

The present invention relates to a modified natural killer (NK) cell and its use in personalised medicine. The modified NK cells of the present invention are non-immunogenic, meaning that they are able to be administered to any recipient subject without being rejected by the host immune system (they are “universal”). In a first embodiment the non-immunogenic NK cells are modified to express CD3 to allow a T-cell Receptor (TcR) to be expressed. In a further embodiment the non-immunogenic NK cells are further modified to express a TcR together with the CD3 co-receptor. Co-expression of CD3 with a specific TcR results in the modified NK cells showing antigen-specific cytotoxicity towards target cells. Universal NK cells can thus be targeted against specific antigens, and may thus be used in personalised medicine, particularly in the field of oncology.

Provided herein are methods of producing natural killer (NK) 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 the NK 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 ce3lls and the NK cell populations produced by the three-stage methods described herein to an individual having the cancer or viral infection.

The present invention relates to a method of using a receptor (e.g., chimeric antigen receptor—CAR) that activates an immune response upon binding a cancer cell ligand in conjunction with a target-binding molecule that targets a protein or molecule CI for removal or neutralization to generate enhanced anti-cancer immune cells. The present invention also relates to engineered immune cells having enhanced therapeutic efficacy and uses thereof.

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. The derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors or additional cells in combination therapies.

Provided herein are immunoresponsive cells having IL-1 superfamily activities with spatiotemporal restriction. The immunoresponsive cells can further express a protease for regulating the IL-1 superfamily activities, and a chimeric antigen receptor (CAR) or a parallel CAR. Also provided herein are methods of preparing the immunoresponsive cells and methods of directing T cell mediated immune response using the immunoresponsive cells.