Compositions and methods for the therapy and diagnosis of lung cancer

Abstract

Compositions and methods for the therapy and diagnosis of cancer, particularly lung cancer, are disclosed. Illustrative compositions comprise one or more lung tumor polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of diseases, particularly lung cancer.

1 . A method for the treatment of a lung cancer in a patient, wherein the lung cancer is characterized by overexpression of the polynucleotide provided in SEQ ID NO:347 or a variant of SEQ ID NO:347 having at least 95% identity to the polynucleotide sequence of SEQ ID NO:347, comprising administering to the patient a polynucleotide comprising the polynucleotide sequence selected from the group consisting of:
 (a) the polynucleotide sequence set forth in SEQ ID NO:347;   (b) the polynucleotide sequence of a variant of SEQ ID NO:347 having at least 95% identity to the polynucleotide sequence of SEQ ID NO:347; and   (c) the polynucleotide sequence of a fragment of the polynucleotide sequence of (a) or (b), wherein the fragment encodes an immunogenic portion of the polypeptide encoded by the polynucleotide of SEQ ID NO:347.   
     
     
         2 . A method for the treatment of a lung cancer in a patient comprising administering to the patient the polynucleotide set forth in SEQ ID NO:347, wherein the lung cancer is characterized by overexpression of the polypeptide provided in SEQ ID NO:347, or a variant of SEQ ID NO:347 having at least 95% identity to the polynucleotide sequence of SEQ ID NO:347. 
     
     
         3 . A method for the treatment of a lung cancer in a patient, wherein the lung cancer is characterized by overexpression of the polynucleotide provided in SEQ ID NO:347, or a variant of SEQ ID NO:347 having at least 95% identity to the polynucleotide sequence of SEQ ID NO:347, comprising administering to the patient a composition comprising a first component selected from the group consisting of physiologically acceptable carriers and immunostimulants and a second component comprising a polynucleotide comprising the polynucleotide sequence set forth in SEQ ID NO:347. 
     
     
         4 . The method of  claim 1 , wherein said polynucleotide encodes a fusion protein. 
     
     
         5 . The method of  claim 4 , wherein the fusion protein comprises a T helper epitope. 
     
     
         6 . The method of  claim 4  wherein the fusion protein comprises a fusion partner selected from the group consisting of: a protein D derivative, a C-terminal domain of the LYTA protein, Ra12, the non-structural protein from influenza virus (NS1), and an endosomal/lysosomal compartment targeting signal. 
     
     
         7 . The method of  claim 3 , wherein said polynucleotide encodes a fusion protein. 
     
     
         8 . The method of  claim 7 , wherein the fusion protein comprises a T helper epitope. 
     
     
         9 . The method of  claim 7  wherein the fusion protein comprises a fusion partner selected from the group consisting of: a protein D derivative, a C-terminal domain of the LYTA protein, Ra12, the non-structural protein from influenza virus (NS1), and an endosomal/lysosomal compartment targeting signal. 
     
     
         10 . The method of  claim 3 , wherein said immunostimulant is an adjuvant that induces a predominantly Th1 type immune response. 
     
     
         11 . The method of  claim 10 , wherein said adjuvant is selected from the group consisting of: 3D-MPL, QS21, a mixture of QS21 and cholesterol, and a CpG oligonucleotide. 
     
     
         12 . The method of any one of  claims 1 - 11  wherein the lung cancer is a lung squamous cell carcinoma or a lung adenocarcinoma. 
     
     
         13 . The method of any one of  claims 1 - 11  wherein said polynucleotide is delivered by a viral based delivery system. 
     
     
         14 . The method of  claim 13  wherein the viral based delivery system comprises an adenovirus. 
     
     
         15 . The method of any one of  claims 1 - 11  wherein said polynucleotide is delivered in a DNA prime/adenovirus boost regimen.