Provided herein are nucleic acids, vectors, and cells containing an expression-optimized codon that encodes a Munc13-4 polypeptide or a STXBP2 polypeptide. Also provided are methods of making and using the nucleic acids, vectors, and cells. Also provided herein are methods of treating of Hemophagocytic Lymphohistiocytosis (HLH) in a subject.

Provided herein are modified NK-92® cells comprising one or more nucleic acids encoding i) a homing receptor, ii) Antigen Binding Protein (ABP) or Chimeric Antigen Recpetor (CAR) that specifically binds to a target antigen, iii) an Fc Receptor such as CD16 or CD16-158V, and/or iv) a cytokine, wherein the nucleic acid sequence is operably linked to a promoter. Further provided herein are modified NK-92® cells comprising one or more nucleic acids encoding i) IL-12 and/or TGF-beta trap, ii) an Antigen Binding Protein (ABP) or Chimeric Antigen Recpetor (CAR) that specifically binds to a target antigen, iii) an Fc Receptor such as CD16 or CD16-158V, and/or iv) a cytokine, wherein the nucleic acid sequence is operably linked to a promoter. Also provided are compositions and kits comprising the modified NK-92® cells, as well as methods of treating cancer using the modified cells.

The invention involves a method for modulating leukocyte activity, comprising delivering to a leukocyte a vector containing nucleic acid molecule(s), whereby the leukocyte contains Cas9 and the vector expresses one or more RNAs to guide the Cas9 to introduce mutations in one or more target genetic loci in the leukocyte, thereby modulating expression of one or more genes expressed in the leukocyte. The invention also involves identifying genes associated with leukocyte responses and experimental modeling of aberrant leukocyte activation and diseases associated with leukocytes by introducing mutations into leukocytes. The invention comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate leukocyte associated diseases.

Provided are methods of making innate immune cell compositions containing gamma.delta (γδ) T cells and/or Natural Killer (NK) cells, and the resulting compositions and related products of manufacture and kits for use in cancer and infectious disease therapy. The methods provided herein permit tailoring of the relative amounts of gamma.delta (γδ) T cells and Natural Killer (NK) cells in the compositions. for cellular therapies against a wide variety of cancers and infectious diseases. The resulting compositions can further be used to generate compositions containing either NK cells alone or gamma.delta T cells alone, for immune cellular therapies. The compositions provided herein also can be genetically altered: the gamma delta T cells and Natural Killer cells are modified to express chimeric antigen receptors (CARs) or exogenous T cell receptors (TCRs), which can be used to target any cell surface molecule either directly or indirectly, e.g., a marker on a cancer cell or an infected cell.

The present invention relates to, inter alia, combinations of compositions which include chimeric proteins that find use in methods for treating disease, such as immunotherapies for cancer and autoimmunity.

This disclosure describes a method to induce HBV infection in cells or animal models with an HBV pregenomic RNA (pgRNA). The method is amenable to multiple genotypes and has excellent signal-to-noise ratios. The method can be used to identify novel anti-HBV agents, measure anti-HBV drug efficiency, and predict drug resistance.

The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.

The present disclosure provides formulations and therapies for treating subjects with elevated levels of TIM-3 using gene-based cytotoxic immunostimulant therapy alone or with other immunotherapies.

The present invention provides methods of negatively modulating the Werner protein (WRN) to inhibit proliferative cells characterized by high microsatellite instability (MSI-H), for example to treat proliferative diseases (such as cancer) characterized by high MSI (MSI-H). Further provided are compositions used in such methods.

Provided is a tetravalent homodimeric bispecific antibody molecule simultaneously targeting an immune effector cell antigen CD3 and a tumor-associated antigen, wherein the bispecific antibody molecule contains, in order from N-terminus to C-terminus, a first single chain Fv, a second single chain Fv and a Fc fragment; wherein the first single chain Fv can specifically bind to the tumor-associated antigen, the second single chain Fv can specifically bind to CD3, and the first and the second single chain Fvs are connected by a linker peptide, while the second single chain Fv and the Fc fragment are directly connected or connected by a linker peptide; and the Fc fragment does not have effector functions such as CDC, ADCC and ADCP.