Anti-CD70 chimeric antigen receptors
The invention provides a chimeric antigen receptor (CAR) having antigenic specificity for CD70, the CAR comprising: an antigen binding-transmembrane domain comprising a CD27 amino acid sequence lacking all or a portion of the CD27 intracellular T cell signaling domain; a 4-1BB intracellular T cell signaling domain; a CD3ζ intracellular T cell signaling domain; and optionally, a CD28 intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, 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 chimeric antigen receptor (CAR) having antigenic specificity for CD70, the CAR comprising:
a CD70 binding—transmembrane domain comprising the amino acid sequence of SEQ ID NO: 3, wherein the CD70 binding—transmembrane domain does not comprise residues 212 to 260 of the amino acid sequence of SEQ ID NO: 2;
a CD3ζ intracellular T cell signaling domain comprising the amino acid sequence of SEQ ID NO: 4; and
one or both of (i) a 4-1BB intracellular T cell signaling domain comprising the amino acid sequence of SEQ ID NO: 5 and (ii) a CD28 intracellular T cell signaling domain comprising the amino acid sequence of SEQ ID NO: 6.
2. The CAR according to claim 1 , comprising the 4-1BB intracellular T cell signaling domain and the CD28 intracellular T cell signaling domain.
3. The CAR according to claim 1 , comprising the 4-1BB intracellular T cell signaling domain.
4. The CAR of claim 1 , comprising the amino acid sequence of any one of SEQ ID NOs: 8-10.
5. A nucleic acid comprising a nucleotide sequence encoding the CAR according to claim 1 .
6. The nucleic acid according to claim 5 , comprising the nucleotide sequence of any one of SEQ ID NOs: 15-17.
7. A recombinant expression vector comprising the nucleic acid of claim 6 .
8. An isolated host cell comprising the recombinant expression vector of claim 7 .
9. An isolated population of cells comprising at least one host cell of claim 8 .
10. A pharmaceutical composition comprising the CAR of claim 1 and a pharmaceutically acceptable carrier.
11. The CAR of claim 4 comprising the amino acid sequence SEQ ID NO: 8.
12. The CAR of claim 4 comprising the amino acid sequence SEQ ID NO: 9.
13. The CAR of claim 4 comprising the amino acid sequence SEQ ID NO: 10.
14. The nucleic acid according to claim 6 , comprising the nucleotide sequence of SEQ ID NO: 15.
15. The nucleic acid according to claim 6 , comprising the nucleotide sequence of SEQ ID NO: 16.
16. The nucleic acid according to claim 6 , comprising the nucleotide sequence of SEQ ID NO: 17.