Chimeric antigen receptor (CAR) that targets chemokine receptor CCR4 and its use
AssigneesThe United States of America, as represented by the Secretary, Department of Health and Human Services, The United States Government as represented by the Department of Veterans Affairs
InventorsLiyanage Parakrama Perera, Thomas Alexander Waldmann, Kevin Charles Conlon, Pin-Yu Perera
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Abstract
A chimeric antigen receptor is disclosed that includes: (a) an scFv comprising a light chain variable domain (VL) and a heavy chain variable domain (VH), wherein the scFv specifically binds to CCR4; (b) a hinge and transmembrane domain from CD8; (c) an intracellular 4-1BB signaling domain; and (d) an intracellular CD3 zeta signaling domain, wherein (a)-(d) are in N to C terminal order. Uses of the chimeric antigen receptor, such as for treating a malignancy, are also disclosed.
Claims27
An isolated nucleic acid molecule encoding a chimeric antigen receptor, wherein the nucleic acid molecule comprises the nucleic acid sequence of SEQ ID NO:
- 11, and wherein the chimeric antigen receptor comprises:
- (a) an extracellular scFv comprising a light chain variable domain (VL) and a heavy chain variable domain (VH), wherein the scFv specifically binds to CCR4, wherein the VH comprises a heavy chain complementarity determining region (HCDR)1, an HCDR2 and an HCDR3, wherein the HCDR1 comprises amino acids 26-33 of SEQ ID NO:
- 1, the HCDR2 comprises amino acids 51-58 of SEQ ID NO:
- 1, and the HCDR3 comprises amino acids 99-107 of SEQ ID NO:
- 1, and wherein the VL comprises a light chain complementarity determining region (LCDR)1, a LCDR2 and a LCDR3, wherein the LCDR1 comprises amino acids 27-38 of SEQ ID NO:
- 2, the LCDR2 comprises amino acids 56-61 of SEQ ID NO:
- 2, and the LCDR3 comprises amino acids 95-102 of SEQ ID NO:
- 2;
- (b) a hinge and transmembrane domain from CD8;
- (c) an intracellular 4-1BB signaling domain;
- (d) an intracellular CD3 zeta signaling domain, wherein (a)-(d) are in N-terminal to C-terminal order, and
- wherein the chimeric antigen receptor further comprises an immunoglobulin signal sequence comprising the amino acid sequence of SEQ ID NO:
- 4.
An isolated nucleic acid molecule encoding the amino acid sequence set forth as SEQ ID NO:
- 10.
An isolated nucleic acid molecule encoding a chimeric antigen receptor,
- wherein the chimeric antigen receptor comprises:
- (a) an extracellular scFv comprising a light chain variable domain (VL) and a heavy chain variable domain (VH), wherein the scFv specifically binds to CCR4, wherein the VH comprises a heavy chain complementarity determining region (HCDR)1, an HCDR2 and an HCDR3, wherein the HCDR1 comprises amino acids 26-33 of SEQ ID NO:
- 1, the HCDR2 comprises amino acids 51-58 of SEQ ID NO:
- 1, and the HCDR3 comprises amino acids 99-107 of SEQ ID NO:
- 1, and wherein the VL comprises a light chain complementarity determining region (LCDR)1, a LCDR2 and a LCDR3, wherein the LCDR1 comprises amino acids 27-38 of SEQ ID NO:
- 2, the LCDR2 comprises amino acids 56-61 of SEQ ID NO:
- 2, and the LCDR3 comprises amino acids 95-102 of SEQ ID NO:
- 2, wherein scFv comprises a linker, and
- (b) a hinge and transmembrane domain from CD8;
- (c) an intracellular 4-1BB signaling domain;
- (d) an intracellular CD3 zeta signaling domain, wherein (a)-(d) are in N-terminal to C-terminal order, and
- wherein the nucleic acid molecule comprises the nucleic acid sequence of SEQ ID NO:
- 14.
Dependencies are inferred from the claim text.