Murine anti-NY-ESO-1 T cell receptors
The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for NY-ESO-1. Also provided are related polypeptides, proteins, nucleic acids, recombinant expression vectors, isolated host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions. The invention further provides a method of detecting the presence of cancer in a mammal and a method of treating or preventing cancer in a mammal using the inventive TCRs or related materials.
1. An isolated or purified T-cell receptor (TCR) having antigenic specificity for NY-ESO-1 (SEQ ID NO: 1) and comprising a murine variable region, wherein the TCR comprises the amino acid sequences of SEQ ID NOs: 3-8.
2. The isolated or purified TCR according to claim 1 , wherein the TCR has antigenic specificity for NY-ESO-1 157-165 (SEQ ID NO: 2).
3. The isolated or purified TCR according to claim 1 , comprising the amino acid sequences of SEQ ID NOs: 9 and 10.
4. The isolated or purified TCR according to claim 1 , comprising the amino acid sequences of SEQ ID NOs: 11 and 12.
5. An isolated or purified polypeptide comprising the amino acid sequences of SEQ ID NOs: 3-8.
6. The isolated or purified polypeptide of claim 5 , comprising the amino acid sequences of both SEQ ID NOs: 9 and 10.
7. The isolated or purified polypeptide of claim 5 , comprising the amino acid sequences of both SEQ ID NOs: 11 and 12.
8. An isolated or purified protein comprising the polypeptide of claim 5 .
9. An isolated or purified protein comprising a first polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 3-5 and a second polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 6-8.
10. The isolated or purified protein according to claim 9 , comprising a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 9 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 10.
11. The isolated or purified protein according to claim 9 , comprising a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 11 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 12.
12. The isolated or purified protein of claim 8 , wherein the protein is a fusion protein.
13. The isolated or purified protein of claim 8 , wherein the protein is a recombinant antibody.
14. An isolated or purified nucleic acid comprising a nucleotide sequence encoding the TCR according to claim 1 .
15. The isolated or purified nucleic acid according to claim 14 , wherein the nucleotide sequence is codon-optimized.
16. The isolated or purified nucleic acid according to claim 14 , wherein the nucleotide sequence comprises both of SEQ ID NOs: 15 and 16 or both of SEQ ID NOs: 19 and 20.
17. A recombinant expression vector comprising the nucleic acid according to claim 14 .
18. The recombinant expression vector according to claim 17 , wherein the nucleotide sequence comprises a nucleotide sequence encoding a complementarity determining region (CDR) 1α, CDR2α, CDR3α, CDR1β, CDR2β, and CDR3β, and the nucleotide sequence encoding the CDR1α, CDR2α, and CDR3α is 5′ of the nucleotide sequence encoding the CDR1β, CDR2β, and CDR3β.
19. The recombinant expression vector according to claim 17 , wherein the nucleotide sequence comprises a nucleotide sequence encoding a CDR 1α, CDR2α, CDR3α, CDR1β, CDR2β, and CDR3β, and the nucleotide sequence encoding the CDR1α, CDR2α, and CDR3α is 3′ of the nucleotide sequence encoding the CDR1β, CDR2β, and CDR3β.
20. The recombinant expression vector according to claim 18 , comprising SEQ ID NO: 17.
21. The recombinant expression vector according to claim 19 , comprising SEQ ID NO: 18.
22. An isolated host cell comprising the recombinant expression vector of claim 17 .
23. The host cell according to claim 22 , wherein the cell is human.
24. A population of cells comprising at least one host cell of claim 22 .
25. A pharmaceutical composition comprising the TCR according to claim 1 , and a pharmaceutically acceptable carrier.
26. A method of detecting the presence of cancer in a mammal, comprising:
(a) contacting a sample comprising one or more cells from the mammal with the TCR according to claim 1 , thereby forming a complex, and
(b) detecting the complex, wherein detection of the complex is indicative of the presence of cancer in the mammal;
wherein the cancer is melanoma, breast cancer, lung cancer, prostate cancer, thyroid cancer, ovarian cancer, or synovial cell sarcoma.
27. A method of treating melanoma in a mammal, the method comprising administering to the mammal the TCR according to claim 1 in an amount effective to treat melanoma in a mammal.