M971 chimeric antigen receptors
The invention provides a chimeric antigen receptor (CAR) comprising an antigen binding domain comprising SEQ ID NOs: 1-6, a transmembrane domain, and an intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.
1. A nucleic acid comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR) comprising (a) an antigen binding domain which binds to CD22 and comprises an amino acid sequence comprising a heavy chain CDR1 comprising SEQ ID NO: 1, a heavy chain CDR2 comprising SEQ ID NO: 2, a heavy chain CDR3 comprising SEQ ID NO: 3, light chain CDR1 comprising SEQ ID NO: 4, a light chain CDR2 comprising SEQ ID NO: 5, and a light chain CDR3 comprising SEQ ID NO: 6, (b) a transmembrane domain, and (c) an intracellular T cell signaling domain.
2. The nucleic acid according to claim 1 , comprising a nucleotide sequence comprising SEQ ID NO: 25.
3. The nucleic acid according to claim 2 , comprising a nucleotide sequence selected from SEQ ID NOs: 26-28.
4. A recombinant expression vector comprising the nucleic acid of claim 1 .
5. An isolated host cell comprising the recombinant expression vector of claim 4 .
6. A population of isolated cells comprising at least one host cell of claim 5 .
7. The nucleic acid according to claim 1 , wherein the antigen binding domain comprising a light chain variable region comprising an amino acid sequence comprising SEQ ID NO: 7.
8. The nucleic acid according to claim 1 , wherein the antigen binding domain comprising a heavy chain variable region comprising an amino acid sequence comprising SEQ ID NO: 8.
9. The nucleic acid according to claim 1 , wherein the antigen binding domain comprising an amino acid sequence comprising SEQ ID NO: 9.
10. The nucleic acid according to claim 1 , wherein the transmembrane domain comprising an amino acid sequence comprising SEQ ID NO: 12 or 18 and/or an amino acid sequence comprising SEQ ID NO: 15.
11. The nucleic acid according to claim 1 , wherein the intracellular T cell signaling domain comprising an amino acid sequence comprising SEQ ID NO: 16 or 19.
12. The nucleic acid according to claim 1 , wherein the intracellular T cell signaling domain comprising an amino acid sequence comprising SEQ ID NO: 13 or 20.
13. The nucleic acid according to claim 1 , wherein the intracellular T cell signaling domain comprising an amino acid sequence comprising SEQ ID NO: 14, 17 or 21.
14. The nucleic acid according to claim 2 , comprising a nucleotide sequence comprising SEQ ED NO: 26.
15. The nucleic acid according to claim 2 , comprising a nucleotide sequence comprising SEQ ID NO: 27.
16. The nucleic acid according to claim 2 , comprising a nucleotide sequence comprising SEQ ID NO: 28.
17. A pharmaceutical composition comprising the host cell of claim 5 , or a population thereof, and a pharmaceutical acceptable carrier, wherein the host cell is a T cell.
18. A method of treating hematological cancer in a human subject, the method comprising administering to the subject a host cell of claim 5 , or a population thereof, in an amount effective to treat the cancer in the subject, wherein the host cell is a T cell.