Anti-SSX-2 T cell receptors and related materials and methods of use
The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for synovial sarcoma X Breakpoint (SSX)-2. The invention further provides related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells. Further provided by the invention are antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention. Methods of detecting the presence of cancer in a host and methods of treating or preventing cancer in a host are further provided by the invention.
1. An isolated or purified T cell receptor (TCR) comprising the amino acid sequences of SEQ ID NOs: 13-18, SEQ ID NO: 21 and SEQ ID NO: 22, wherein
the TCR has antigenic specificity for synovial sarcoma X Breakpoint (SSX)-2 (SEQ ID NO: 1) presented in the context of an HLA-A2 molecule,
wherein the TCR also recognizes SSX-4 (SEQ ID NO: 4), and
wherein the TCR is a human/mouse chimeric TCR.
2. The TCR of claim 1 , wherein the TCR also recognizes any one or more of SSX-3 (SEQ ID NO: 3), SSX-5 (SEQ ID NO: 5), SSX-9 (SEQ ID NO: 6), and SSX-10 (SEQ ID NO: 7).
3. The TCR of claim 1 , wherein the TCR has antigenic specificity for an SSX-2 peptide comprising KASEKIFYV (SEQ ID NO: 2).
4. The TCR of claim 1 , wherein the TCR recognizes any one or more of KVSEKIVYV (SEQ ID NO: 8), KSSEKIVYV (SEQ ID NO: 9), KASEKHYV (SEQ ID NO: 10), KSSEKIIYV (SEQ ID NO: 11), and KASEKILYV (SEQ ID NO: 12).
5. The TCR of claim 1 , wherein the TCR comprises SEQ ID NOs: 19 and 20.
6. The TCR of claim 1 , wherein the TCR comprises SEQ ID NO: 25 and 26.
7. An isolated or purified polypeptide comprising a functional portion of the TCR of claim 1 , wherein the functional portion comprises the amino acid sequences of SEQ ID NOs: 13-18.
8. The isolated or purified polypeptide of claim 7 , wherein the portion comprises the amino acid sequences of SEQ ID NOs: 19 and 20.
9. The isolated or purified polypeptide of claim 8 , comprising:
a) SEQ ID NO: 23 and 24; or
b) SEQ ID NO: 25 and 26.
10. An isolated or purified protein comprising a first polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 13-15 and SEQ ID NO: 21 and a second polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 16-18 and SEQ ID NO: 22, wherein the protein is a human/mouse chimeric protein.
11. The isolated or purified protein of claim 10 , wherein the first polypeptide chain comprises SEQ ID NO: 19 and the second polypeptide chain SEQ ID NO: 20.
12. The isolated or purified protein of claim 11 , wherein the first polypeptide chain comprises SEQ ID NO: 25 and the second polypeptide chain comprises SEQ ID NO: 26.
13. The isolated or purified protein of claim 10 , wherein the protein is a fusion protein.
14. The isolated or purified protein of claim 10 , wherein the protein is a recombinant antibody.
15. A composition comprising the TCR of claim 1 and a pharmaceutically acceptable carrier.
16. A composition comprising the TCR of claim 5 and a pharmaceutically acceptable carrier.
17. A composition comprising the TCR of claim 6 and a pharmaceutically acceptable carrier.
18. A composition comprising the polypeptide of claim 7 and a pharmaceutically acceptable carrier.
19. A composition comprising the polypeptide of claim 8 and a pharmaceutically acceptable carrier.
20. A composition comprising the polypeptide of claim 9 and a pharmaceutically acceptable carrier.
21. A composition comprising the protein of claim 10 and a pharmaceutically acceptable carrier.
22. A composition comprising the protein of claim 11 and a pharmaceutically acceptable carrier.
23. A composition comprising the protein of claim 12 and a pharmaceutically acceptable carrier.