Disclosed are compositions and methods related to the construction and use of conditional universal synthetic notch (synNotch) receptors and conditional chimeric antigen receptor (CAR) T cells. Also disclosed herein are methods of using said synNotch receptors in the construction of engineered cells. It is contemplated herein that the disclosed synNotch receptors and engineered cells can be used in regenerative medicine. Additionally disclosed herein are methods of using the disclosed synNotch, CAR T cells, and engineered cells in the treatment of cancer, autoimmune disease, autoinflammatory disease, and infectious disease.

The invention described herein provide Kaposi Sarcoma-Associated Herpesvirus (KSHV) oncoprotein antigens and epitopes for expanding antigen-specific T cells. Such expanded T cells are useful for, e.g., in allogeneic or off-the-shelf adoptive T cell therapy.

A method of manipulating allogeneic cells for use in allogeneic cell therapy providing a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism, or Mirror Effect. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the mirror of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The mirror of the GVH effect is the host vs. graft (HVG) effect The anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used to stimulate host immunity in a complete HLA mis-matched setting in a patient.

Provided are a universal T cell and preparation method thereof. The universal T cells comprise CAR-T and TCR-T cells, and are obtained by knocking out TCR and/or HLA and/or PD-1 proteins of T cells by a CRISPR/Cas9 genome editing technology, wherein the universal CAR-T continues to kill target cells in vivo and in vitro.

Disclosed herein are methods and compositions for treating cancer by eliciting an immune response by administering dendritic cells expressing heterologous proteins. In some embodiments, a dendritic cell comprises one or more heterologous nucleic acid molecules encoding for CD40L and CXCL13. In some embodiments, the dendritic cell further comprises a heterologous nucleic acid molecule encoding for CD93. In yet additional embodiments, the dendritic cells expressing heterologous proteins are activated.

Provided are methods and compositions for use in cancer immunotherapies. In various embodiments, the compositions include functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. In various embodiments, 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 in combination therapies.

The present invention relates to an engineered immune cell which comprises: (i) a target binding polypeptide comprising a target-binding domain and a first protein interaction domain, and (ii) a localising polypeptide comprising a second protein interaction domain, which binds to the first protein binding domain, and an intracellular retention signal. When the target binding polypeptide binds its target protein and also the localising polypeptide, expression of the target protein at the cell surface is reduced or eliminated because the target protein is retained in an intracellular compartment.

The present disclosure relates to the field of cell therapy, and more specifically, to improving CAR and/or TCR function through cytokine signaling or cytokine receptor signaling.

Provided herein are methods of treating a solid malignant tumor using antigen-specific T cells and methods of managing tumor flare in treatment of a solid malignant tumor using antigen-specific T cells. The methods provided herein improve the safety of treatment by informing the patient about the potential risks for tumor flare, telling the patient to contact his or her physician if tumor swelling occurs, counseling a patient with Waldeyer's ring lymphadenopathy to contact his or her physician if shortness of breath or stridor occurs, or grading and managing tumor flare developed in the patient.

The present invention relates to genetically modified B cells and their uses thereof, for example, for the treatment of a variety of diseases and disorders, including cancer, heart disease, inflammatory disease, muscle wasting disease, neurological disease, and the like. In certain embodiments, the invention relates to an isolated modified B cell (CAR-B cell), capable of expressing a chimeric receptor (CAR-B receptor), wherein said chimeric receptor comprises (a) an extracellular domain; (b) a transmembrane domain; and (c) a cytoplasmic domain that comprises at least one signaling domain. In various embodiments, the invention comprises an isolated modified B cell, wherein said B cell is capable of expressing and secreting a payload, wherein the payload is not naturally expressed in a B cell or is expressed at higher levels than is naturally expressed in a B cell. In various embodiments, the payload is an antibody or fragment thereof.