Antibody having a t-cell receptor-like specificity, yet higher affinity, and the use of same in the detection and treatment of cancer, viral infection and autoimmune disease

Abstract

An isolated molecule which comprises an antibody specifically bindable with a binding affinity below 20 nanomolar, preferably below 10 nanomolar, to a human major histocompatibility complex (MHC) class I being complexed with a HLA-restricted antigen and optionally further comprises an identifiable or therapeutic moiety conjugated to the antibody.

1 . An isolated soluble antibody specifically bindable with a binding affinity below 20 nanomolar to a human major histocompatibility complex (MHC) class I protein complexed with a HLA-restricted antigen, wherein said soluble antibody binds viral infected cells or tumor cells naturally presenting said human MHC class I complexed with said HLA-restricted antigen. 
     
     
         2 . The antibody of  claim 1 , wherein said HLA-restricted antigen is from tyrosinase. 
     
     
         3 . The isolated soluble antibody of  claim 1 , further comprising an identifiable moiety being conjugated to said antibody. 
     
     
         4 . The isolated soluble antibody of  claim 1 , further comprising a therapeutic moiety being conjugated to said antibody. 
     
     
         5 . The isolated antibody of  claim 1 , wherein said binding is evidenced by FACS. 
     
     
         6 . A pharmaceutical composition comprising the soluble antibody of  claim 1 . 
     
     
         7 . The pharmaceutical composition of  claim 6 , wherein said antibody further comprises a therapeutic moiety conjugated to said antibody. 
     
     
         8 . A diagnostic composition comprising the soluble antibody of  claim 1 . 
     
     
         9 . An isolated molecule comprising a polynucleotide encoding the antibody of  claim 1 . 
     
     
         10 . A method of producing the antibody of  claim 1 , the method comprising:
 immunizing a genetically engineered non-human mammal having cells expressing said human major histocompatibility complex (MHC) class I with a soluble form of a MHC class I molecule being complexed with said HLA-restricted antigen;   isolating mRNA molecules from antibody producing cells of said non-human mammal;   producing a phage display library displaying protein molecules encoded by said mRNA molecules; and   isolating at least one phage from said phage display library, said at least one phage displaying said antibody specifically bindable with said affinity below 20 nanomolar to said human major histocompatibility complex (MHC) class I being complexed with said HLA-restricted antigen.   
     
     
         11 . The method of  claim 10 , wherein said non-human mammal is devoid of self MHC class I molecules. 
     
     
         12 . A method of treating a cancer, the method comprising administering to a subject in need thereof a therapeutically effective amount of the antibody of  claim 1 , thereby treating cancer in the subject. 
     
     
         13 . The method of  claim 12 , wherein said HLA-restricted antigen is from Tyrosinase. 
     
     
         14 . The method of  claim 13 , wherein said cancer comprises melanoma.