Abstract: Methods are provided for treating a subject for an EGFRvIII expressing glioblastoma. The methods of the present disclosure involve administering to the subject a molecular circuit that is primed by EGFRvIII to induce one or more encoded therapeutics specific for one or more antigens expressed by the glioblastoma. 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: Methods are provided for treating a subject for an EGFRvIII expressing glioblastoma. The methods of the present disclosure involve administering to the subject a molecular circuit that is primed by EGFRvIII to induce one or more encoded therapeutics specific for one or more antigens expressed by the glioblastoma. 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: Methods are provided for treating a subject for glioblastoma, including e.g., an EGFRvIII negative glioblastoma. The methods of the present disclosure involve administering to a subject a molecular circuit that includes a binding triggered transcriptional switch (BT'S) that binds to a priming antigen expressed by the subjects glioblastoma multiforme (GBM) that, when bound to the priming antigen, induces one or more encoded therapeutics specific for one or more antigens expressed by the GBM. 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: Methods are provided for treating a subject for glioblastoma, including e.g., an EGFRvIII negative glioblastoma. The methods of the present disclosure involve administering to a subject a molecular circuit that includes a binding triggered transcriptional switch (BTTS) that binds to a priming antigen expressed by the subjects glioblastoma multiforme (GBM) that, when bound to the priming antigen, induces one or more encoded therapeutics specific for one or more antigens expressed by the GBM. 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: The present disclosure relates generally to the field of immunology, and particularly relates to hybrid chimeric antigen receptors designed to combine fast time-scale intracellular signal transduction and long time-scale transcription regulation. 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 an activity of a cell and/or for the treatment of various health conditions or diseases, such as cancers.

Abstract: Provided are chimeric polypeptides which modulate various cellular processes following cleavage of a force sensor cleavage domain, including non-Notch force sensor cleavage domains, induced upon binding of a specific binding member of the chimeric polypeptide with its binding partner. Methods of using force sensor cleavage domain-containing chimeric polypeptides to modulate cellular functions, including e.g., modulation (including induction or repression) 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 monitoring cell-cell signaling and method of treating a subject using the described components, as well as kits for practicing the subject methods.

Abstract: Provided herein is a cell comprising a recombinant nucleic acid encoding a transmembrane protein that has an extracellular binding domain that specifically binds to a brain-selective extracellular antigen, e.g., MOG, CDH10, PTPRZ1 or NRCAM, wherein the cell does not comprise a nucleic acid encoding an antigen-specific therapeutic that binds to a killing antigen expressed by a glioblastoma.

Abstract: A method for treating a subject for glioblastoma is provided. In some embodiments, the method may comprise administering to a subject a molecular circuit that includes a binding triggered transcriptional switch (BTTS) that, when bound to MOG, induces one or more encoded therapeutics specific for one or more antigens expressed by the GBM. 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: Methods are provided for treating a subject for glioblastoma, including e.g., an EGFRvIII negative glioblastoma. The methods of the present disclosure involve administering to a subject a molecular circuit that includes a binding triggered transcriptional switch (BTTS) that binds to a priming antigen expressed by the subjects glioblastoma multiforme (GBM) that, when bound to the priming antigen, induces one or more encoded therapeutics specific for one or more antigens expressed by the GBM. 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: Methods are provided for treating a subject for an EGFRvIII expressing glioblastoma. The methods of the present closure involve administering to the subject a molecular circuit that is primed by EGFRvIII to induce one or more encoded therapeutics specific for one or more antigens expressed by the glioblastoma. 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 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 polypeptides which modulate various cellular processes following cleavage of a force sensor cleavage domain, including non-Notch force sensor cleavage domains, induced upon binding of a specific binding member of the chimeric polypeptide with its binding partner. Methods of using force sensor cleavage domain-containing chimeric polypeptides to modulate cellular functions, including e.g., modulation (including induction or repression) 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 monitoring cell-cell signaling and method of treating a subject using the described components, as well as kits for practicing the subject methods.