The present disclosure relates to compositions and methods for using cells having chemically-induced fusion protein complexes to spatially and temporally control immune cell signal initiation and downstream responses for treating disease. As a preferred example, the present disclosure relates to fusion polypeptides comprising (a) a first polypeptide comprising a first secretion signal, a first multimerization domain, a first transmembrane domain, and an actuator domain, (b) a viral self-cleaving polypeptide, and (c) a second polypeptide comprising a second secretion signal, a binding domain that comprises a single chain antibody, a receptor ectodomain, or a ligand, a second multimerization domain, and a second transmembrane domain.

The present invention provides gene editing systems comprising gene editing dimerization switches comprising a first and second gene editing switch domain that allow for the regulation of a gene editing function by the introduction, e.g., administration, of a gene editing dimerization molecule having the ability to bring together a first gene editing switch domain and a second gene editing switch domain. A regulated gene editing function provides, e.g., less off-target side effects, and increases the therapeutic window.

The present invention also provides improved FKBP/FRB-based dimerization switches wherein the FRB switch domain or the FKBP switch domain, or both the FRB and FKBP switch domains, comprise one or more mutations that optimize performance, e.g., that alter, e.g., enhance the formation of a complex between the first switch domain, the second switch domain, and the dimerization molecule, rapamycin, or a rapalog, e.g., RAD001.

The present disclosure provides compositions and methods related to transcription factor systems. Such systems provide for modular and tunable protein expression driven by regulated transcriptional activity.

The present disclosure provides a heterodimeric, conditionally active chimeric antigen receptor (CAR), and a nucleic acid comprising a nucleotide sequence encoding the CAR. The present disclosure provides cells genetically modified to produce the CAR. A CAR of the present disclosure can be used in various methods, which are also provided.

The present disclosure provides adoptive T cell therapies that have improved DARIC architectures for targeting tumor antigens and recruiting TCR signaling complexes for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

The present invention relates to a novel human epidermal growth factor (hEGF)-trigger factor (TF) fusion protein and a use thereof. More particularly, the human epidermal growth factor (hEGF)-trigger factor (TF) fusion protein of the present invention has fused therein: a signal peptide of a Bacillus subtilis-derived xylanase; a human epidermal growth factor (hEGF); and an Escherichia coli-derived trigger factor (TF). Therefore, the present invention not only enhances the water solubility and expression rate of a target protein, but also notably enhances useful effects such as the effects of increasing skin cell growth and healing a wound, and thus may be widely used in various industries as an active ingredient for a functional cosmetic composition and a pharmaceutical composition.

The present invention provides biocircuit systems, effector modules and compositions for cancer immunotherapy. Methods for inducing anti-cancer immune responses in a subject are also provided.

Aspects of the disclosure relate to compositions and methods for regulation of transgene (e.g., miRNAs, shRNAs or coding sequences) expression from viral vectors. In some embodiments, the disclosure provides expression constructs comprising a viral vector encoding one or more transgenes, the expression of which is regulated by a rapamycin/rapalog-based system.

Compositions and methods are provided for depletion of pluripotent cells. In one embodiment of the invention, methods are provided for depletion of pluripotent cells from a mixed population of differentiated cells and stem cells, to provide a population of cells substantially free of pluripotent stem cells.

The present disclosure provides a heterodimeric, conditionally active chimeric antigen receptor (CAR), and a nucleic acid comprising a nucleotide sequence encoding the CAR. The present disclosure provides cells genetically modified to produce the CAR. A CAR of the present disclosure can be used in various methods, which are also provided.