Switchable non-scFv chimeric receptors, switches, and methods of use thereof to treat cancer
AssigneeThe Scripps Research Institute
InventorsTravis Young, Chanhyuk Kim, Peter G. Schultz
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Abstract
Disclosed herein are switchable chimeric receptors, switchable chimeric receptor effector cells and chimeric receptor effector cell switches. The switchable chimeric receptor-ECs are generally T cells. The chimeric receptors have non-antibody extracellular domains that recognize a chimeric receptor binding partner on the chimeric receptor-EC switch or target cell. The chimeric receptor-ECs and switches may be used for the treatment of a disease or condition in a subject in need thereof.
Claims16
A chimeric receptor comprising:
- a. a non-antibody extracellular domain comprising a first peptide capable of forming an alpha helix that binds to a chimeric receptor binding peptide;
- b. transmembrane domain;
- and
- c. intracellular signaling domain,
- wherein the intracellular signaling domain signals to the chimeric receptor effector cell on which the chimeric receptor is expressed when the non-antibody extracellular domain binds to the chimeric receptor binding peptide;
- and
- wherein the chimeric receptor binding peptide comprises a second peptide capable of forming an alpha helix and binding to the first peptide.
A kit comprising:
- a. a chimeric receptor-effector cell switch comprising:
- 1) a chimeric receptor binding peptide comprising a first peptide capable of forming an alpha helix and binding to a non-antibody extracellular domain of a chimeric receptor on an effector cell;
- and
- 2) a targeting moiety that interacts with a cell surface molecule on a target cell;
- and
- b. a chimeric receptor-effector cell comprising a chimeric receptor that comprises:
- 1) a non-antibody extracellular domain comprising a second peptide capable of forming an alpha helix that binds to the alpha helix of the first peptide;
- 2) a transmembrane domain;
- and
- 3) an intracellular signaling domain,
- wherein the intracellular signaling domain signals to the chimeric receptor effector cell when the first peptide binds to the second peptide.
A method of treating cancer in a subject in need thereof, comprising:
- A. administering to the subject a chimeric receptor-effector cell comprising:
- i. a chimeric receptor comprising:
- a. a non-antibody extracellular domain comprising a first peptide capable of forming an alpha helix that binds to a second peptide capable of forming an alpha helix, wherein the second peptide present on a chimeric receptor-effector cell switch;
- b. a transmembrane domain;
- and
- c. an intracellular signaling domain, wherein the intracellular signaling domain signals to the chimeric receptor effector cell on which the chimeric receptor is expressed when the non-antibody extracellular domain binds to the chimeric receptor binding peptide;
- and
- B. administering to the subject the chimeric receptor-effector cell switch;
- said switch comprising:
- i. the chimeric receptor binding peptide comprising the second peptide;
- and
- ii. a targeting moiety that interacts with a cell surface molecule on a target cell.
Dependencies are inferred from the claim text.