T cell receptors recognizing hla-a1- or hla-cw7-restricted mage

Abstract

The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for a) melanoma antigen family A (MAGE A)-3 in the context of HLA-A1 or b) MAGE-A12 in the context of HLA-Cw7. 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) having antigenic specificity for a) melanoma antigen family A (MAGE A)-3 in the context of HLA-A1 or b) MAGE-A12 in the context of HLA-Cw7. 
     
     
         2 . The isolated or purified TCR of  claim 1  having antigenic specificity for a) a MAGE-A3 epitope comprising EVDPIGHLY (SEQ ID NO: 2) or b) a MAGE-A12 epitope comprising VRIGHLYIL (SEQ ID NO: 4). 
     
     
         3 . The isolated or purified TCR of  claim 2 , comprising the amino acid sequences of SEQ ID NOs: 5-10, 16-21, 26-31, or 36-41. 
     
     
         4 . The isolated or purified TCR of  claim 3 , comprising the amino acid sequences of SEQ ID NOs: 11-12, 22-23, 32-33, or 42-43. 
     
     
         5 . The isolated or purified TCR of  claim 4 , comprising the amino acid sequences of SEQ ID NOs: 13-14, 24-25, 34-35, or 44-45. 
     
     
         6 . 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: 5-10, 16-21, 26-31, or 36-41. 
     
     
         7 . The isolated or purified polypeptide of  claim 6 , wherein the portion comprises the amino acid sequences of SEQ ID NOs: 11-12, 22-23, 32-33, or 42-43. 
     
     
         8 . The isolated or purified polypeptide of  claim 7 , wherein the portion comprises the amino acid sequences of SEQ ID NOs: 13-14, 24-25, 34-35, or 44-45. 
     
     
         9 . An isolated or purified protein comprising at least one of the polypeptides of  claim 6 . 
     
     
         10 . The isolated or purified protein of  claim 9 , comprising:
 a first polypeptide chain comprising the amino acid sequence of SEQ ID NOs: 5-7, 16-18, 26-28, or 36-38; and   a second polypeptide chain comprising the amino acid sequence of SEQ ID NOs: 8-10, 19-21, 29-31, or 39-41.   
     
     
         11 . The isolated or purified protein of  claim 10 , comprising:
 a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 11, 22, 32, or 42; and   a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 12, 23, 33, or 43.   
     
     
         12 . The isolated or purified protein of  claim 11 , comprising:
 a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 13, 24, 34, or 44; and   a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 14, 25, 35, or 45.   
     
     
         13 . The protein of  claim 9 , wherein the protein is a fusion protein. 
     
     
         14 . The protein of  claim 9 , wherein the protein is a recombinant antibody. 
     
     
         15 . An isolated or purified nucleic acid comprising a nucleotide sequence encoding the TCR of  claim 1 . 
     
     
         16 . The nucleic acid of  claim 15 , comprising a nucleotide sequence comprising any of SEQ ID NOs: 46-49. 
     
     
         17 . An isolated or purified nucleic acid comprising a nucleotide sequence which is complementary to the nucleotide sequence of the nucleic acid of  claim 16 . 
     
     
         18 . An isolated or purified nucleic acid comprising a nucleotide sequence which hybridizes under stringent conditions to the nucleotide sequence of the nucleic acid of  claim 15 . 
     
     
         19 . A recombinant expression vector comprising the nucleic acid of  claim 15 . 
     
     
         20 . An isolated host cell comprising the recombinant expression vector of  claim 19 . 
     
     
         21 . The isolated host cell of  claim 20 , wherein the cell is a peripheral blood lymphocyte (PBL). 
     
     
         22 . The isolated host cell of  claim 21 , wherein the PBL is a T cell. 
     
     
         23 . The isolated host cell of  claim 20 , wherein the cell is a tumor infiltrating lymphocyte (TIL). 
     
     
         24 . A population of cells comprising at least one host cell of  claim 20 . 
     
     
         25 . An antibody, or antigen binding portion thereof, which specifically binds to a functional portion of the TCR of  claim 1 , wherein the functional portion comprises the amino acid sequences of SEQ ID NOs: 5-10, 16-21, 26-31, or 36-41. 
     
     
         26 . A pharmaceutical composition comprising the TCR of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         27 . A method of detecting the presence of cancer in a host, comprising:
 (i) contacting a sample comprising cells of the cancer with the TCR of  claim 1 , thereby forming a complex, and   (ii) detecting the complex,   wherein detection of the complex is indicative of the presence of cancer in the host.   
     
     
         28 . A method of treating or preventing cancer in a host, comprising administering to the host the TCR of  claim 1 , in an amount effective to treat or prevent cancer in the host. 
     
     
         29 . The method of  claim 27 , wherein the cancer is melanoma, breast cancer, leukemia, thyroid cancer, gastric cancer, pancreatic cancer, liver cancer, lung cancer, ovarian cancer, multiple myeloma, esophageal cancer, kidney cancer, head cancers, neck cancers, prostate cancer, or urothelial cancer. 
     
     
         30 . The method of  claim 27 , wherein the host cell is a cell that is autologous to the host. 
     
     
         31 . The method of  claim 27 , wherein the cells of the population are cells that are autologous to the host. 
     
     
         32 - 35 . (canceled)