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AssigneeThe Regents of the University of California
InventorsWendell A. Lim, Rogelio A. Hernandez-Lopez
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Provided are antigen-density sensing molecular circuits and methods of using the same. Aspects of such circuits will generally include an antigen-triggered switch component and a therapeutic component specific for the same antigen as the antigen-triggered switch component. The circuits will generally be configured such that expression of the therapeutic component is induced by the antigen-triggered switch component when the switch is activated by binding the antigen. Nucleic acids, expression constructs, vectors and the like encoding such circuits, and cells genetically modified to include an antigen-density sensing molecular circuit are also provided. Also provided are methods of making antigen-density sensing molecular circuits, methods of inducing expression of high affinity therapeutics specific to an antigen expressed by a target cell, methods of activating an immune response to a target cell, methods of treating a subject for a cancer expressing an antigen, and the like, where such methods involve antigen-density sensing molecular circuits.
An antigen-density sensing molecular circuit comprising:
The molecular circuit according to any of the preceding claims, wherein the antigen-specific therapeutic comprises a single antigen-binding domain specific for the antigen.
The molecular circuit according to any of the preceding claims, wherein the antigen-triggered transcriptional switch comprises a single antigen-binding domain specific for the antigen.
The molecular circuit according to any of the preceding claims, wherein the antigen-specific therapeutic is a chimeric antigen receptor (CAR), a T cell receptor (TCR), or an antibody.
The molecular circuit according to any of the preceding claims, wherein the antigen-triggered transcriptional switch comprises a Notch force sensor cleavage domain.
A cell genetically modified to comprise the molecular circuit of any of the preceding claims.
A method of making an antigen-density sensing molecular circuit, the method comprising:
A method of inducing expression of a high affinity therapeutic specific to an antigen expressed by a target cell in a subject in need thereof, the method comprising:
A method of activating an immune response to a target cell expressing an antigen in a subject;
A method of treating a subject for a cancer expressing an antigen, the method comprising:
Dependencies are inferred from the claim text.