Chimeric receptors and methods of use thereof
AssigneeSenti Biosciences, Inc.
InventorsBrian Scott Garrison, Michelle Elizabeth Hung, Nicholas Frankel
Life of this patent
Estimating the term…
Abstract
Provided herein are EMCN-specific antigen-binding domains, and chimeric proteins including the EMCN-specific antigen-binding. Also provided herein are cells, nucleic acids, vectors, compositions, and methods directed to proteins including the EMCN-specific antigen-binding domains.
Claims20
A method of stimulating a cell-mediated immune response to a tumor cell in a subject in need thereof comprising administering to the subject a therapeutically effective dose of an isolated cell, the isolated cell comprising an inhibitory chimeric antigen receptor (iCAR) comprising an antigen-binding domain specific for endomucin (EMCN),
- wherein the antigen-binding domain comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein:
- (a) the VH comprises:
- a heavy chain complementarity determining region 1 (CDR-H1) comprising SEQ ID NO:
- 102, a CDR-H2 comprising SEQ ID NO:
- 103, and a CDR-H3 comprising SEQ ID NO:
- 4, and the VL comprises:
- a light chain complementarity determining region 1 (CDR-L1) comprising SEQ ID NO:
- 10, a CDR-L2 comprising SEQ ID NO:
- 11, and a CDR-L3 comprising SEQ ID NO:
- 12, or
- (b) the VH comprises:
- a CDR-H1 comprising SEQ ID NO:
- 2, a CDR-H2 comprising SEQ ID NO:
- 3, and a CDR-H3 comprising SEQ ID NO:
- 4, and the VL comprises:
- a CDR-L1 comprising SEQ ID NO:
- 10, a CDR-L2 comprising SEQ ID NO:
- 11, and a CDR-L3 comprising SEQ ID NO:
- 12.
A method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective dose of an isolated cell, the isolated cell comprising:
- (i) an inhibitory chimeric antigen receptor (iCAR) comprising an antigen-binding domain specific for endomucin (EMCN),
- wherein the antigen-binding domain comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein:
- (a) the VH comprises:
- a heavy chain complementarity determining region 1 (CDR-H1) comprising SEQ ID NO:
- 102, a CDR-H2 comprising SEQ ID NO:
- 103, and a CDR-H3 comprising SEQ ID NO:
- 4, and the VL comprises:
- a light chain complementarity determining region 1 (CDR-L1) comprising SEQ ID NO:
- 10, a CDR-L2 comprising SEQ ID NO:
- 11, and a CDR-L3 comprising SEQ ID NO:
- 12, or
- (b) the VH comprises:
- a CDR-H1 comprising SEQ ID NO:
- 2, a CDR-H2 comprising SEQ ID NO:
- 3, and a CDR-H3 comprising SEQ ID NO:
- 4, and the VL comprises:
- a CDR-L1 comprising SEQ ID NO:
- 10, a CDR-L2 comprising SEQ ID NO:
- 11, and a CDR-L3 comprising SEQ ID NO:
- 12, and
- (ii) one or more tumor-targeting activating CARs (aCARs).
A method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective dose of an isolated cell, the isolated cell comprising:
- (i) an inhibitory chimeric antigen receptor (iCAR) comprising an antigen-binding domain specific for endomucin (EMCN),
- wherein the antigen-binding domain comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein:
- (a) the VH comprises:
- a heavy chain complementarity determining region 1 (CDR-H1) comprising SEQ ID NO:
- 102, a CDR-H2 comprising SEQ ID NO:
- 103, and a CDR-H3 comprising SEQ ID NO:
- 4, and the VL comprises:
- a light chain complementarity determining region 1 (CDR-L1) comprising SEQ ID NO:
- 10, a CDR-L2 comprising SEQ ID NO:
- 11, and a CDR-L3 comprising SEQ ID NO:
- 12, or
- (b) the VH comprises:
- a CDR-H1 comprising SEQ ID NO:
- 2, a CDR-H2 comprising SEQ ID NO:
- 3, and a CDR-H3 comprising SEQ ID NO:
- 4, and the VL comprises:
- a CDR-L1 comprising SEQ ID NO:
- 10, a CDR-L2 comprising SEQ ID NO:
- 11, and a CDR-L3 comprising SEQ ID NO:
- 12, and
- (ii) one or more tumor-targeting activating CARs (aCARs), wherein the one or more aCARs comprise an aCAR that targets FLT3 and/or an aCAR that targets CD33.
Dependencies are inferred from the claim text.