Abstract: Provided herein is an in-series synthetic receptor circuit for dual-antigen AND-gate control over expression of a therapeutic payload by engineered cells. In some embodiments, the circuit may be composed of a first binding-triggered transcriptional switch, a second binding-triggered transcriptional switch and a therapeutic payload (e.g., a chimeric antigen receptor), where binding of the first binding-triggered transcriptional switch to a first antigen activates expression of the second binding-triggered transcriptional switch, and binding of the second binding-triggered transcriptional switch to a second antigen activates expression of the therapeutic payload. If the cell is an immune cell and the therapeutic payload is a chimeric antigen receptor, then the immune cell may be activated by binding of the chimeric antigen receptor to a third antigen. Methods of treatment using the cell also provided.

Abstract: The instant disclosure provides chimeric polypeptides which modulate various cellular processes following a cleavage event induced upon binding of a specific binding member of the polypeptide with its binding partner. Methods of using chimeric polypeptides to modulate cellular functions, including e.g., induction of gene expression, are also provided. Nucleic acids encoding the subject chimeric polypeptides and associated expression cassettes and vectors as well as cells that contain such nucleic acids and/or expression cassettes and vectors are provided. Also provided, are methods of treating a subject using the described components and methods as well as kits for practicing the subject methods.

Abstract: The instant disclosure provides chimeric polypeptides which modulate various cellular processes following a cleavage event induced upon binding of a specific binding member of the polypeptide with its binding partner. Methods of using chimeric polypeptides to modulate cellular functions, including e.g., induction of gene expression, are also provided. Nucleic acids encoding the subject chimeric polypeptides and associated expression cassettes and vectors as well as cells that contain such nucleic acids and/or expression cassettes and vectors are provided. Also provided, are methods of treating a subject using the described components and methods as well as kits for practicing the subject methods.

Abstract: Provided are methods of modulating the survival of therapeutic cells as well as cells and nucleic acids and vectors useful in such methods. Such survival modulation may include enhancing survival and/or enhancing death of the therapeutic cells. The provided methods include administering a therapeutic cell, nucleic acid and/or vector to a subject, the administered therapeutic cells, nucleic acids and/or vectors including one or more heterologous apoptosis modulating agents and/or one or more encoding sequences thereof. Cells of the disclosure include or encode one or more heterologous apoptosis modulating agents.

Abstract: The present disclosure provides polymeric particles comprising biomolecules of interest attached thereto, methods for using the same, and methods for making the same. The surface of the polymeric particles can be functionalized by attaching multiple different biomolecules of interest in a desired ratio for co-presentation. In addition, the polymeric particles may also encapsulate bio-molecules, such as, therapeutic nucleic acids, peptide and/or polypeptides for release in vivo. The present disclosure also provide synthetic particles and methods for enhancing proliferation of CAR-T cells. Additionally, the present disclosure provide biomolecule-coated films and methods.

Abstract: The present disclosure provides heteromeric, conditionally repressible synthetic immune cell receptors, nucleic acids expressing such receptors, cells expressing such nucleic acids and methods of making and using such receptors and nucleic acids. The present disclosure also provides methods of repressing immune cell activation attributable to a stimulatory synthetic immune cell receptor by dimerizing the stimulatory synthetic immune cell receptor with a synthetic immune cell repressor.

Abstract: Provided are methods of treating a subject for a heterogeneous cancer. The methods of the present disclosure include integrating at least two antigens expressed heterogeneously in the cancer and/or in the cancer microenvironment, including where the antigens are expressed in trans, i.e., expressed by at least two different cell types. The subject methods will generally involve immune cells into which circuits have been introduced that employ one or more binding triggered transcriptional switches and one or more encoded therapeutics specific for antigens expressed by cancer cells and/or by neighboring non-cancer cells. Nucleic acids containing sequences encoding all or portions of such circuits are also provided, as well as cells, expression cassettes and vectors that contain such nucleic acids. Also provided are kits for practicing the described methods.

Abstract: Provided are chimeric T cell antigen receptors (TCR) comprising modified TCR chains. The modified TCR chains include fusion polypeptides having one or more heterologous antigen-binding domains fused to the extracellular domain of the TCR chain. Modified TCR chains also include chains that are modified in various other ways including e.g., chain truncation, cysteine modification, domain swapping and combinations thereof. Also provided are nucleic acids encoding the modified TCR chains as well as nucleic acids encoding the chimeric TCRs and recombinant expression vectors comprising such nucleic acids. Immune cells that are genetically modified or otherwise include the described chimeric TCRs, recombinant expression vectors encoding chimeric TCRs, and/or the described nucleic acids are also provided. Methods are also provided, such as methods of killing a target cell and/or treating a subject for a condition, e.g.

Abstract: The instant disclosure provides chimeric polypeptides which modulate various cellular processes following a cleavage event induced upon binding of a specific binding member of the polypeptide with its binding partner. Methods of using chimeric polypeptides to modulate cellular functions, including e.g., induction of gene expression, are also provided. Nucleic acids encoding the subject chimeric polypeptides and associated expression cassettes and vectors as well as cells that contain such nucleic acids and/or expression cassettes and vectors are provided. Also provided, are methods of treating a subject using the described components and methods as well as kits for practicing the subject methods.

Abstract: Polycaprolactone (PCL) scaffolds having macropores interconnected with micorpores are provided. Tissue grafts that include the PCL scaffold having therapeutic cells encapsulated within the macropores are also provided. Also provided are methods of making the PCL scaffold and the tissue graft, and methods of transplanting cells into an individual using the tissue graft.