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.

What is claimed is:  
     
         1 . A method for stimulating and/or expanding T cells specific for a tumor protein, comprising contacting T cells with at least one component selected from the group consisting of: 
 (a) a polypeptide comprising an amino acid sequence set forth in any on of SEQ ID NOs:809, 1934, 1964, 1966-1968, 2005-2011, 2012-2033, 2041-2050, and 2151-2157 or an immunogenic fragment thereof;    (b) a polypeptide consisting of an amino acid sequence set forth in any on of SEQ ID NOs:809, 1934, 1964, 1966-1968, 2005-2011, 2012-2033, 2041-2050, and 2151-2157 or an immunogenic fragment thereof;    (c) a polypeptide having an amino acid sequence at least 90% identity to a polypeptide of (a) or (b);    (d) a polypeptide having an amino acid sequence at least 95% identity to a polypeptide of (a) or (b);    (e) a polynucleotide which encodes a polypeptide having an amino acid sequence as provided in (a), (b), (c) or (d);    (f) a polynucleotide having a sequence provided in SEQ ID NO:1933;    (g) a complement of the sequence provided in SEQ ID NO:1933;    (h) sequences that hybridize to a sequence provided in SEQ ID NO:1933, under highly stringent conditions;    (i) sequences having at least 90% identity to a sequence of SEQ ID NO:1933;    (j) sequences having at least 95% identity to a sequence of SEQ ID NO:1933;    (k) degenerate variants of a sequence provided in SEQ ID NO:1933; and    (m) antigen-presenting cells that express a polypeptide according to (a), (b), (c) or (d),    under conditions and for a time sufficient to permit the stimulation and/or expansion of T cells.    
     
     
         2 . An isolated T cell population, comprising T cells prepared according to the method of  claim 1 .  
     
     
         3 . An isolated polynucleotide comprising a sequence selected from the group consisting of: 
 (a) a sequence provided in SEQ ID NO:1931, 1938, 1941, 1974-2002, 2003, 2105, 2107, 2109, 2111, 2113, 2115, and 2117;    (b) complement of the sequence provided in SEQ ID NO:1931, 1938, 1941, 1974-2002, 2003, 2105, 2107, 2109, 2111, 2113, 2115, and 2117;    (c) sequences consisting of at least 20 contiguous residues of a sequence provided in SEQ ID NO:1931, 1938, 1941, 1974-2002, 2003, 2105, 2107, 2109, 2111, 2113, 2115, and 2117;    (d) sequences that hybridize to a sequence provided in SEQ ID NO:1931, 1938, 1941, 1974-2002, 2003, 2105, 2107, 2109, 2111, 2113, 2115, and 2117 under highly stringent conditions;    (e) sequences having at least 75% identity to a sequence of SEQ ID NO:1931, 1938, 1941, 1974-2002, 2003, 2105, 2107, 2109, 2111, 2113, 2115, and 2117;    (f) sequences having at least 90% identity to a sequence of SEQ ID NO:1931, 1938, 1941, 1974-2002, 2003, 2105, 2107, 2109, 2111, 2113, 2115, and 2117; and    (g) degenerate variants of a sequence provided in SEQ ID NO:1931, 1938, 1941, 1974-2002, 2003, 2105, 2107, 2109, 2111, 2113, 2115, and 2117.    
     
     
         4 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) SEQ ID NO:1927-1930, 1932, 1934, 1937, 1940, 1942-1973, 2004, 2005-2011, 2022-2026, 2028-2033, 2094, 2095, 2102-2104, 2106, 2108, 2110, 2112, 2114, and 2116;    (b) sequences having at least 70% identity to the amino acid sequence as provided in SEQ ID NO:1927-1930, 1932, 1934, 1937, 1940, 1942-1973, 2004, 2005-2-11, 2022-2026, 2028-2033, 2094, 2095, 2102-2104, 2106, 2108, 2110, 2112, 2114, and 2116;    (c) sequences having at least 90% identity to the amino acid sequence as provided in SEQ ID NO:1927-1930, 1932, 1934, 1937, 1940, 1942-1973, 2004, 2005-2-11, 2022-2026, 2028-2033, 2094, 2095, 2102-2104, 2106, 2108, 2110, 2112, 2114, and 2116;    (d) sequences encoded by a polynucleotide of  claim 1;     (e) sequences having at least 70% identity to a sequence encoded by a polynucleotide of  claim 1;  and    (f) sequences having at least 90% identity to a sequence encoded by a polynucleotide of  claim 1 .    
     
     
         5 . An expression vector comprising a polynucleotide of  claim 3  or a polynucleotide which encodes a polypeptide of  claim 4  operably linked to an expression control sequence.  
     
     
         6 . A host cell transformed or transfected with an expression vector according to  claim 5 .  
     
     
         7 . An isolated antibody, or antigen-binding fragment thereof, that specifically binds to a polypeptide selected from the group consisting: 
 (a) a polypeptide according to  claim 4;  and    (b) a polypeptide having an amino acid sequence that is encoded by a polynucleotide sequence provided in SEQ ID NO:1948-1951, 1959, 1962-1968 and 1971 or a complement thereof.    
     
     
         8 . An isolated antibody or antigent-binding fragment thereof according to  claim 7 , wherein the polypeptide is provided in SEQ ID NO:1927-1929 and 1942-1973.  
     
     
         9 . A method for detecting the presence of a cancer in a patient, comprising the steps of: 
 (a) obtaining a biological sample from the patient;    (b) contacting the biological sample with a binding agent that binds to a polypeptide selected from the group consisting of: 
 (i) a polypeptide of  claim 4 ,  
 (ii) a polypeptide having an amino acid sequence provided in SEQ ID NO:1934,  
 (iii) a polypeptide having at least 90% identity to an amino acid sequence provided in SEQ ID NO:1934,  
 (iv) a polypeptide having at least 95% identity to an amino acid sequence provided in SEQ ID NO:1934,  
 (v) a polypeptide encoded by a polynucleotide provided in SEQ ID NO:1933, and  
 (vi) a polypeptide encoded by a polynucleotide having at least 90% identity to a sequence provided in SEQ ID NO:1933;  
   (c) detecting in the sample an amount of polypeptide that binds to the binding agent; and    (d) comparing the amount of polypeptide to a predetermined cut-off value and therefrom determining the presence of a cancer in the patient.    
     
     
         10 . A fusion protein comprising at least one polypeptide selected from the group consisting of: 
 (i) a polypeptide of  claim 4 ,    (ii) a polypeptide having an amino acid sequence provided in SEQ ID NO:1934,    (iii) a polypeptide having at least 90% identity to an amino acid sequence provided in SEQ ID NO:1934,    (iv) a polypeptide having at least 95% identity to an amino acid sequence provided in SEQ ID NO:1934,    (v) a polypeptide encoded by a polynucleotide provided in SEQ ID NO:1933, and    (vi) a polypeptide encoded by a polynucleotide having at least 90% identity to a sequence provided in SEQ ID NO:1933.    
     
     
         11 . A fusion protein according to  claim 10 , wherein the at least one polypeptide is provided in: 
 (a) SEQ ID NO:1937 and 1940; and    (b) a polypeptide encoded by a polynucleotide provided in SEQ ID NO:1938 and 1941.    
     
     
         12 . An oligonucleotide that hybridizes to at least one sequence selected from the group consisting of: 
 (a) a sequence set forth in  claim 3;  and    (b) a sequence provided in SEQ ID NO:1933,    under highly stringent conditions.    
     
     
         13 . A composition comprising a first component selected from the group consisting of physiologically acceptable carriers and immunostimulants, and a second component selected from the group consisting of: 
 (a) polypeptides according to  claim 4;     (b) a polypeptide having an amino acid sequence provided in SEQ ID NO:1934;    (c) a polypeptide having an amino acid sequence with at least 90% identity to SEQ ID NO:1934;    (d) a polypeptide having an amino acid sequence with at least 95% identity to SEQ ID NO:1934;    (e) a polynucleotide according to  claim 3;     (f) a polynucleotide which encodes a polypeptide having an amino acid sequence as provided in (b), (c) or (d);    (g) a polynucleotide having a sequence provided in SEQ ID NO:1933;    (h) complement of the sequence provided in SEQ ID NO:1933;    (i) sequences that hybridize to a sequence provided in SEQ ID NO:1933, under highly stringent conditions;    (j) sequences having at least 90% identity to a sequence of SEQ ID NO:1933;    (k) sequences having at least 95% identity to a sequence of SEQ ID NO:1933;    (1) degenerate variants of a sequence provided in SEQ ID NO:1933;    (m) antibodies according to  claim 7;     (n) fusion proteins according to  claim 10;     (O) T cell populations according to  claim 2;  and    (p) antigen presenting cells that express a polypeptide according to (a), (b), (c) or (d).    
     
     
         14 . A method for stimulating an immune response in a patient, comprising administering to the patient a composition of  claim 13 .  
     
     
         15 . A method for the treatment of a lung cancer in a patient, comprising administering to the patient a composition of  claim 13 .  
     
     
         16 . A method for determining the presence of a cancer in a patient, comprising the steps of: 
 (a) obtaining a biological sample from the patient;    (b) contacting the biological sample with an oligonucleotide according to  claim 2;     (c) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; and    (d) compare the amount of polynucleotide that hybridizes to the oligonucleotide to a predetermined cut-off value, and therefrom determining the presence of the cancer in the patient.    
     
     
         17 . A diagnostic kit comprising at least one oligonucleotide according to  claim 12 .  
     
     
         18 . A diagnostic kit comprising at least one antibody according to  claim 7  and a detection reagent, wherein the detection reagent comprises a reporter group.  
     
     
         19 . A method for inhibiting the development of a lung cancer in a patient, comprising the steps of: 
 (a) incubating CD4+ and/or CD8+ T cells isolated from a patient with at least one component selected from the group consisting of: 
 (i) polypeptides according to  claim 4;   
 (ii) a polypeptide having an amino acid sequence provided in SEQ ID NO:1934,  
 (iii) a polypeptide having an amino acid sequence with at least 90% identity to SEQ ID NO:1934,  
 (iv) a polypeptide having an amino acid sequence with at least 95% identity to SEQ ID NO:1934,  
 (v) polynucleotides according to  claim 3 ,  
 (vi) a polynucleotide which encodes a polypeptide having an amino acid sequence as provided in (i), (ii), (iii) or (iv),  
 (vii) a polynucleotide having a sequence provided in SEQ ID NO:1933,  
 (viii) complement of the sequence provided in SEQ ID NO:1933,  
 (ix) sequences that hybridize to a sequence provided in SEQ ID NO:1933, under highly stringent conditions,  
 (x) sequences having at least 90% identity to a sequence of SEQ ID NO:1933,  
 (xi) sequences having at least 95% identity to a sequence of SEQ ID NO:1933,  
 (xii) degenerate variants of a sequence provided in SEQ ID NO:1933, and  
 (xiii) antigen presenting cells that express a polypeptide according to (i), (ii), (iii) or (iv),  
   such that T cells proliferate;    (b) administering to the patient an effective amount of the proliferated T cells; and thereby inhibiting the development of a cancer in the patient.    
     
     
         20 . A method of detecting the presence of a cancer in a patient, comprising the steps of: 
 (a) obtaining a biological sample fom the patient;    (b) contacting the biological sample with a polypeptide comprising an amino acid sequence having at least 90% identity to a sequence set forth in any one of SEQ ID NOs: 809, 1812, 1813, or an immunogenic fragment thereof;    (c) detecting in the sample an amount of antibody that binds to the polypeptide; and    (d) comparing the amount of antibody to a predetermined cut-off value and therefrom determining the presence of a cancer in the patient.    
     
     
         21 . The method of  claim 20  wherein the immunogenic fragment is selected from the group consisting of: 2012, 2013, 2015, 2025, 2021, 2028, 2035- 2037, 2047, 2059, 2061, 2069, 2071, 2073, 2076, 2082, 2096, 2097, 2100, 2119, 2120, 2125 2127, 2128, 2139- 2141, 2142, 2151-2154, 2156, and 2157.  
     
     
         22 . An isolated antibody, or antigen-binding fragment thereof, that specifically binds to a polypeptide having an amino acid sequence set forth in SEQ ID NOs: 1874 or 2004.  
     
     
         23 . The isolated antibody or antigen-binding fragment thereof according to  claim 22 , wherein the antibody or antigen-binding fragment thereof is coupled to a therapeutic agent.  
     
     
         24 . The isolated antibody or antigen-binding fragment thereof according to  claim 23 , wherein the antibody is a monoclonal antibody.