Anti-SLAMF7 chimeric antigen receptors
View Patent ↗Provided are chimeric antigen receptors (CARs) having antigenic specificity for B-cell Maturation Antigen (SLAMF7). Also provided are related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs. Methods of treating or preventing cancer in a mammal are also provided.
1. A nucleic acid comprising:
(a) a suicide gene; and
(b) a nucleotide sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises a single chain comprising an antigen recognition domain, a transmembrane (TM) domain, and a T cell activation domain, wherein the CAR has antigenic specificity for signaling lymphocyte activating molecule F7 (SLAMF7), wherein the TM domain comprises a TM domain of CD8α or CD28, wherein the antigen recognition domain comprises the amino acid sequences of SEQ ID NOs: 1-6;
wherein the nucleotide sequence encoding the CAR is positioned 3′ of the suicide gene, and wherein the suicide gene is an inducible caspase 9 (IC9) gene.
2. The nucleic acid of claim 1 , wherein the antigen recognition domain comprises the amino acid sequences of
SEQ ID NOs: 13-14.
3. The nucleic acid of claim 1 , wherein the T-cell activation domain comprises a T-cell signaling domain of any one of the following proteins: a human CD28 protein, a human CD3-zeta protein, a human FcRγ protein, a CD27 protein, an OX40 protein, a human 4-1BB protein, a human inducible T-cell costimulatory protein (ICOS), modified versions of any of the foregoing, or any combination of the foregoing.
4. The nucleic acid of claim 1 , further comprising a nucleotide sequence encoding a cleavable linker sequence.
5. The nucleic acid of claim 4 , wherein the nucleotide sequence encoding the cleavable linker sequence is positioned between the nucleotide sequence encoding the CAR and the suicide gene.
6. The nucleic acid of claim 1 , wherein the nucleotide sequence encodes the amino acid sequence of any one of SEQ ID NOs: 27, 29 and 31.
7. The nucleic acid according to claim 1 , wherein the TM domain consists of a TM domain of CD8α or CD28.
8. A vector comprising the nucleic acid of claim 1 .
9. An isolated host cell comprising the vector of claim 8 .
10. The isolated host cell of claim 9 , wherein the host cell is a T-cell.
11. The isolated host cell of claim 9 , wherein the host cell is a natural killer (NK) cell.
12. A population of cells comprising at least one host cell of claim 9 .
13. A method of treating or preventing cancer in a mammal, the method comprising administering to the mammal the nucleic acid of claim 1 , in an amount effective to treat or prevent cancer in the mammal.
14. The method according to claim 13 , wherein the cancer is multiple myeloma.
15. A nucleic acid comprising:
(a) a suicide gene; and
(b) a nucleotide sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises a single chain comprising, from the N-terminus to the C-terminus: a CD8α signal sequence, an antigen recognition domain, a human CD8 α hinge and transmembrane domain, a cytoplasmic portion of human CD28, and a cytoplasmic portion of human CD3ζ,
wherein the CAR has antigenic specificity for signaling lymphocyte activating molecule F7 (SLAM F7),
wherein the antigen recognition domain comprises the amino acid sequences of SEQ ID NOs: 1-6;
wherein the nucleotide sequence encoding the CAR is positioned 3′ of the suicide gene, and wherein the suicide gene is an inducible caspase 9 (IC9) gene.
16. The nucleic acid of claim 15 , wherein the antigen recognition domain comprises the amino acid sequences of SEQ ID NOs: 13-14.