Compounds that either produced a higher proportion or greater absolute number of phenotypically identified nave, stem cell memory, central memory T cells, adaptive NK cells, and type I NKT cells are identified. Compositions and methods for modulating immune cells including T, NK, and NKT cells for adoptive cell therapies with improved efficacy are provided.

Methods and compositions for modifying T-cells in which PD1 and/or CTLA-4 is repressed and/or inactivated using fusion proteins such as artificial transcription factors and nucleases.

The present disclosure generally relates to, inter alia, a class of chimeric switch receptors containing an endodomain of an IL-9 receptor, engineered to modulate transcriptional regulation in a ligand-dependent manner. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating gene expression, modulating an activity of a cell, and/or for the treatment of various health conditions or diseases.

Provided are humanized anti-HLA-A2 antibodies. In certain aspects, the humanized anti-HLA-A2 antibodies are capable of constituting an antigen binding domain of a chimeric antigen receptor (CAR), where the CAR is capable of being expressed in a human cell such that the CAR specifically binds to HLA-A2. Also provided are CARs that include the humanized anti-HLA-A2 antibodies. Modified cells including the antibodies and CARs, as well as methods of using such modified cells are also provided.

The current disclosure describes simplified methods of preparing cells for patient infusion where the simplified methods result utilize less steps than conventional methods, decreasing required manipulation steps and reducing the time between beginning of cell manipulation for administration and ultimate administration to a patient. Methods of cryopreserving, thawing, and diluting cells and kits for practicing the methods are also provided herein.

The present disclosure provides genetically modified autologous and/or allogenic B cell compositions and methods for treatment of cancer and/or metastatic cancer. B cells are modified ex vivo. The genetically modified B cell express at least one therapeutic protein, wherein the modified B cell is CD38+, CD138+, CD78+, IL-6R+, and CD27++ and wherein the modified B cell is capable of homing to bone marrow for improved efficacy of cancer treatment. In typical embodiments, the therapeutic protein is capable of binding a tumor associated antigen (TAA) located within the bone-localized cancer. The administered modified B cell composition can express and release the therapeutic protein at the cancer site, typically within bone.

Provided are genetically modified NK cells expressing a chimeric antigen receptor targeting an EGFR superfamily receptor. The CAR can comprise an intracellular domain of FcRI and further recombinant proteins expressed by the genetically modified NK cells are CD16, autocrine growth stimulating cytokines, and optionally one of IL-12, a TGF-beta trap, or a homing receptor. Also described are methods for treating a patient having or suspected of having a disease that is treatable with NK-92 cells, such as cancer, comprising administering to the patient the genetically modified NK cells.

The present invention is in the field of cell-based immunotherapies. In particular, the invention provides a modified cell comprising a first and second polypeptide forming an antigen-binding site at the external side of the cell, and a polypeptide comprising a signaling domain, wherein, upon binding of the antigen-binding site to a corresponding antigen, the signaling domain triggers a process in the cell that enables the cell to promote death of a target cell comprising said antigen on the cell surface. The invention also provides medical uses of the modified cell, in particular for use in the treatment of diseases. Furthermore, the invention provides a kit comprising at least one nucleic acid molecule encoding said polypeptides, and methods for producing the modified cells of the invention. In addition, the invention provides chimeric polypeptides and nucleic acid molecules encoding chimeric polypeptides.

The present invention includes compositions and methods for modifying a T cell with a nucleic acid encoding a switch molecule comprising an extracellular domain comprising a membrane receptor or fragment thereof and an intracellular domain comprising a signaling receptor or fragment thereof. In one aspect, a method comprises introducing a nucleic acid encoding a switch molecule and a nucleic acid encoding a soluble fusion protein and/or a nucleic acid encoding a bispecific antibody into a population of cells comprising T cells, wherein the T cells transiently expresses the switch molecule and soluble fusion protein or bispecific antibody. In other aspect, compositions of T cells and methods of treating a disease or condition, such as cancer or an autoimmune disease, are also included.

The present disclosure generally relates to, inter alia, a class of chimeric switch receptors containing an endodomain of an IL-9 receptor, engineered to modulate transcriptional regulation in a ligand-dependent manner. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating gene expression, modulating an activity of a cell, and/or for the treatment of various health conditions or diseases.