Human leukocyte antigen restricted gamma delta t cell receptors and methods of use thereof

Abstract

Disclosed herein are compositions and methods of treating a subject with cancer. The compositions and methods utilize immunoresponsive cells to effect killing of tumor cells.

What is claimed is: 
     
         1 . A method comprising: administering to a subject a composition that comprises a polypeptide construct or a functional fragment thereof or a cell that comprises the polypeptide construct or said functional fragment thereof, wherein said polypeptide construct or said functional fragment thereof comprises a y-TCR polypeptide and a 45-TCR polypeptide, wherein said polypeptide construct or said functional fragment thereof binds a first human leukocyte antigen (HLA) molecule of serotype HLA-A*24 on an aberrant cell when said HLA molecule is in an HLA complex with at least a second HLA molecule, and wherein said aberrant cell is a cancer cell or a cell infected with a pathogen. 
     
     
         2 . The method of  claim 1 , wherein said HLA-A*24 is HLA-A*24:02. 
     
     
         3 . The method of  claim 1 , wherein said HLA complex is formed selectively on at least one of said cancer cell or said cell infected with said pathogen as compared to non-cancer cells or cells not infected with said pathogen. 
     
     
         4 . The method of  claim 1 , wherein said polypeptide construct of said functional fragment thereof binds said HLA complex in the presence of at least one co-receptor selected from a group consisting of: CD8, CD4, CD28, C—C chemokine receptor (CCR), and C—X—C chemokine receptor type 4 (CXCR4). 
     
     
         5 . The method of  claim 1 , wherein said polypeptide construct or functional fragment thereof is ectopically expressed on an immune cell. 
     
     
         6 . The method of  claim 5 , wherein said immune cell is an αβT-cell. 
     
     
         7 . The method of  claim 1 , wherein said polypeptide construct or said functional fragment thereof is in soluble form. 
     
     
         8 . The method of  claim 1 , wherein said polypeptide construct or said functional fragment thereof comprises a gamma delta T cell receptor (γδTCR). 
     
     
         9 . The method of  claim 1 , wherein said γ-TCR polypeptide and said δ-TCR polypeptide are 7962. 
     
     
         10 . The method of  claim 1 , wherein said γ-TCR polypeptide and said δ-TCR polypeptide are 7561. 
     
     
         11 . The method of  claim 1 , wherein a CDR3 in said γ-TCR polypeptide comprises a sequence comprising 90% identity to any one of SEQ ID NO: 2 and SEQ ID NO: 239 to SEQ ID NO: 428. 
     
     
         12 . The method of  claim 1 , wherein a CDR3 of said δ-TCR polypeptide comprises a sequence comprising 90% identity to any one of SEQ ID NO: 3 and SEQ ID NO: 7 to SEQ ID NO: 237. 
     
     
         13 . The method of  claim 1 , wherein a sequence coding for said γ-TCR polypeptide comprises at least 90% identity to residues 19-309 of SEQ ID NO: 4. 
     
     
         14 . The method of  claim 1 , wherein a sequence coding for said δ-TCR polypeptide comprises at least 90% identity to residues 21-293 of SEQ ID NO: 5.