Soluble tcr molecules and methods of use

Abstract

Disclosed are compositions and methods for detecting cells or tissue comprising a peptide antigen presented in the context of an MHC or HLA complex. The invention has a wide range of applications including providing a highly sensitive method for detecting cancer cells.

1 - 38 . (canceled) 
     
     
         39 . A soluble single-chain T cell receptor fusion molecule comprising a T cell receptor and a biologically active polypeptide or fragment thereof connected by a first peptide linker,
 wherein the soluble single-chain T cell receptor has one recognition binding site and the biologically active polypeptide or fragment thereof has a different recognition binding site,   wherein the soluble single-chain T cell receptor comprises an α variable chain and a β variable chain T cell receptor (TCR) covalently linked together by a second peptide linker and a β constant domain covalently linked to the β variable chain,   wherein the soluble single-chain T cell receptor specifically binds to SEQ ID NO: 1; and   wherein the biologically active polypeptide or fragment thereof is an IL-2 cytokine or a fragment thereof.   
     
     
         40 . The soluble single chain T cell receptor fusion molecule of  claim 39  wherein the fusion molecule comprises a sequence of covalently linked subunits comprising the sequence: (NH2)-TCR-Vα-second peptide linker-TCR-Vβ-TCR-Cβ-first peptide linker-biologically active polypeptide or fragment thereof. 
     
     
         41 . The soluble T cell receptor fusion molecule of  claim 39  wherein the biologically active polypeptide or fragment thereof is specific for recognition of an effector cell. 
     
     
         42 . The soluble single-chain T cell receptor fusion molecule of  claim 39  wherein at least one of the first and second peptide linkers includes from about 7 to 20 amino acids. 
     
     
         43 . The soluble single-chain T cell receptor fusion molecule of  claim 39  wherein the first and second peptide linkers includes from about 8 to 16 amino acids. 
     
     
         44 . The soluble single-chain T cell receptor fusion molecule of  claim 43 , wherein at least one of the first and second peptide linkers consist of alanine, serine and glycine to provide for flexibility. 
     
     
         45 . A therapeutic composition for treatment of disorders comprising a therapeutically effective amount of the T cell receptor fusion molecule of  claim 39  and a sterile, pharmaceutically acceptable carrier vehicle.