The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors. The signals of the activating and blocking receptors can be modulated via the identity of a hinge.

The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, that exhibit cross-talk between the receptors.

Provided are antibodies, fragments thereof, chimeric antigen receptors (CARs) and T cell receptors (TCRs) comprising one or more of the anti-PMCA antigen binding domains disclosed herein. SynNotch receptors that comprise an anti-PSCA binding domain Provided are polynucleotides encoding antibodies, fragments thereof, CARs, T cell receptors (TCR) and SynNotch receptors. Provided are compositions, cells and cell therapies comprising the same. Further provided are methods of treatment.

Compositions containing multiple different AAV stock are provided which allow for regulated expression of an immunoglobulin in a variety of tissues. Also provided is a method for regulating the dose of a pharmacologically active immunoglobulin. The method involves co-administering: (a) a first stock of recombinant AAV containing: an activation domain operably linked to expression control sequences comprising a promoter and a first nuclear localization signal; and a DNA binding domain comprising a zinc finger homeodomain and two or more FK506 binding protein domain (FKBP) subunit genes, wherein a first FKBP subunit gene and a second FKBP subunit gene have coding sequences which are no more than about 85% identical to each other, said DNA binding domain being operably linked to a second nuclear localization signal; and (b) a second stock of recombinant AAV comprising at least 2 to about 12 copies of a zinc finger homeodomain which are specific binding partners for the zinc finger homeodomain of the DNA binding domain, and further comprising at least one immunoglobulin expression cassette operably linked to inducible expression control sequences, such that when an effective amount of a rapamycin or rapalog is delivered transcription and expression of the immunoglobulin gene is induced.

The invention relates to a novel ligand inducible polypeptide coupling system and methods of modulating cell signal transduction pathways and other intracellular and extracellular protein-protein interactions.

This invention relates to the field of therapeutics. Disclosed are methods of generating conditionally expressing erythropoietin under the control of an ecdysone receptor-based gene expression modulation system in the presence of activating ligand and uses for therapeutic purposes in animals. The methods of the invention cause an in vivo increase in the expression of erythropoietin and an increase in the hematocrit or volume percentage of red blood cells in blood after administration of the ligand.

Provided are chimeric receptors for engineering cells for adoptive therapy, including T cells, and the genetically engineered cells. In some aspects, also provided are methods and compositions for engineering and producing the cells, compositions containing the cells, and method for their administration to subjects. In some embodiments, the cells, such as T cells, contain genetically engineered antigen receptors that specifically bind to antigens, such as a chimeric antigen receptor (CAR), and which contain an intracellular signaling domain capable of inducing TRAF6-mediated signaling. In some embodiments, features of the cells and methods provide for increased or improved activity, efficacy and/or persistence.

Methods to create chemically-induced dimerizing (CID) protein systems and uses thereof are described. The methods utilize antibody binding domain dimerizing proteins. The created systems can be used to regulate cellular events such as gene expression, receptor signaling and cell death to effectuate a variety of clinically relevant treatment outcomes.

The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, that exhibit cross-talk between the receptors.

The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, in which the blocking receptor provides a signal that dominates a signal from the activating receptor.