Ii-KEY/HER-2/NEU HYBRID CANCER VACCINE

Abstract

Provided are methods and compositions for treating cancer in humans, the cancer being characterized by expression of Her-2/neu. The methods involve vaccinating a patient with an Ii-Key/MHC class II hybrid construct and thereby stimulating an immune response to the native Her-2/neu protein. The construct may be in the form of an Ii-Key hybrid peptide or a nucleic acid encoding an Ii-Key hybrid peptide. Methods are described wherein the cancer being treated is breast cancer. Also claimed is a pharmaceutical composition comprising an Ii-Key/MHC class II hybrid construct with and without an adjuvant. The adjuvant can include GM-CSF. The Ii-Key hybrid construct includes the LRMK [SEQ ID NO.: 2] residues of Ii-Key protein and an MHC Class II epitope of a protein or portion thereof which is used in the vaccine or a DNA encoding the same hybrid peptide.

1 . A method of treating a cancer in humans, the cancer being characterized by expression of Her-2/neu, comprising:
 a) providing an li-Key/MHC class II hybrid construct in an immunoadjuvant-free pharmaceutically acceptable carrier, the construct consisting essentially of:
 i) an MHC class II epitope-containing segment of Her-2/neu consisting of the sequence GVGSPYVSRLLGICL [SEQ ID NO.: 3] linked at its N-terminus to the LRMK [SEQ ID NO.: 2] amino acid residues of li protein; or 
 ii) DNA encoding i); and 
   b) stimulating a patient's immune system by vaccination with the hybrid construct of step a) under conditions appropriate for the stimulation of an immune response.   
     
     
         2 . The method of  claim 1  which is characterized by the stimulation of CD4+ T cell production. 
     
     
         3 . The method of  claim 1  which is characterized by the stimulation of a CD4+ T cell response specific to native Her-2/neu peptide. 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1  wherein the cancer is breast, ovary, recto-colon, lung, prostate, stomach, pancreatic, or biliary cancer. 
     
     
         7 . The method of  claim 1  wherein the cancer is breast cancer. 
     
     
         8 . (canceled) 
     
     
         9 . A pharmaceutical composition for use in the treatment of cancer, the pharmaceutical composition comprising an li-Key/MHC Class II hybrid construct in an immunoadjuvant-free pharmaceutically acceptable carrier, the li-Key/MHC Class II hybrid construct consisting essentially of:
 a) an MHC Class II epitope-containing segment of Her-2/neu consisting of the sequence GVGSPYVSRLLGICL [SEQ ID NO.: 3] linked at its N-terminus to the LRMK [SEQ ID NO.:2] residues of the li protein; or   b) DNA encoding a).   
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein said an li-Key/MHC class II hybrid construct is administered to said patient at a dose of about 100 μg to about 1000 μg. 
     
     
         14 . The method of  claim 1 , wherein said patent is vaccinated with said li-Key/MHC class II hybrid construct in multiple sequential doses.