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 . An isolated polynucleotide comprising a sequence selected from the group consisting of:
 (a) sequences provided in SEQ ID NO:1-323, 341-782, 784-785, 788, 790, 792, 794, 796, 800-804, 807, 808, 810-826, 828-1664, 1668, 1669, 1676, 1680-1805, 1823, 1824, 1826-1829, 1861, 1862, 1865-1868, 1873, 1875, 1877, 1879, 1881, 1883, 1891-1900, 1910, 1914, 1918, 1922-1924, 1931, 1933, 1938, 1941, 1974-2002, 2003, 2034-2040, 2105, 2107, 2109, 2111, 2113, 2115, and 2117;   (b) complements of the sequences provided in SEQ ID NO:1-323, 341-782, 784-785, 788, 790, 792, 794, 796, 800-804, 807, 808, 810-826, 828-1664, 1668, 1669, 1676, 1680-1805, 1823, 1824, 1826-1829, 1861, 1862, 1865-1868, 1873, 1875, 1877, 1879, 1881, 1883, 1891-1900, 1910, 1914, 1918, 1922-1924, 1931, 1933, 1938, 1941, 1974-2002, 2003, 2034-2040, 2105, 2107, 2109, 2111, 2113, 2115, and 2117;   (c) sequences comprising or consisting of at least 10, 20, 25, 30, 35, 40, 45, 50, 75 and 100 contiguous residues of a sequence provided in SEQ ID NO:1-323, 341-782, 784-785, 788, 790, 792, 794, 796, 800-804, 807, 808, 810-826, 828-1664, 1668, 1669, 1676, 1680-1805, 1823, 1824, 1826-1829, 1861, 1862, 1865-1868, 1873, 1875, 1877, 1879, 1881, 1883, 1891-1900, 1910, 1914, 1918, 1922-1924, 1931, 1933, 1938, 1941, 1974-2002, 2003, 2034-2040, 2105, 2107, 2109, 2111, 2113, 2115, and 2117;   (d) sequences that hybridize to a sequence provided in SEQ ID NO:1-323, 341-782, 784-785, 788, 790, 792, 794, 796, 800-804, 807, 808, 810-826, 828-1664, 1668, 1669, 1676, 1680-1805, 1823, 1824, 1826-1829, 1861, 1862, 1865-1868, 1873, 1875, 1877, 1879, 1881, 1883, 1891-1900, 1910, 1914, 1918, 1922-1924, 1931, 1933, 1938, 1941, 1974-2002, 2003, 2034-2040, 2105, 2107, 2109, 2111, 2113, 2115, and 2117, under moderate or highly stringent conditions;   (e) sequences having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity to a sequence of SEQ ID NO:1-323, 341-782, 784-785, 788, 790, 792, 794, 796, 800-804, 807, 808, 810-826, 828-1664, 1668, 1669, 1676, 1680-1805, 1823, 1824, 1826-1829, 1861, 1862, 1865-1868, 1873, 1875, 1877, 1879, 1881, 1883, 1891-1900, 1910, 1914, 1918, 1922-1924, 1931, 1933, 1938, 1941, 1974-2002, 2003, 2034-2040, 2105, 2107, 2109, 2111, 2113, 2115, and 2117;   (f) degenerate variants of a sequence provided in SEQ ID NO:1-323, 341-782, 784-785, 788, 790, 792, 794, 796, 800-804, 807, 808, 810-826, 828-1664, 1668, 1669, 1676, 1680-1805, 1823, 1824, 1826-1829, 1861, 1862, 1865-1868, 1873, 1875, 1877, 1879, 1881, 1883, 1891-1900, 1910, 1914, 1918, 1922-1924, 1931, 1933, 1938, 1941, 1974-2002, 2003, 2034-2040, 2105, 2107, 2109, 2111, 2113, 2115, and 2117.   
     
     
         2 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:
 (a) SEQ ID NO:324-340, 783, 786, 787, 789, 791, 793, 795, 797-799, 805, 806, 809, 827, 1667, 1670-1675, 1677-1679, 1806-1822, 1825, 1830-1833, 1834-1856, 1863, 1864, 1869-1872, 1874, 1876, 1878, 1880, 1882, 1884-1890, 1901-1909, 1913, 1917, 1921, 1925-1930, 1932, 1934, 1937, 1940, 1942-1973, 2004, 2005-2011, 2012-2033, 2041-2050, 2094, 2095, 2102-2104, 2106, 2108, 2110, 2112, 2114, 2116, and 2119-2157;   (b) sequences having at least 70% identity to the amino acid sequence as provided in SEQ ID NO:324-340, 783, 786, 787, 789, 791, 793, 795, 797-799, 805, 806, 809, 827, 1667, 1670-1675, 1677-1679, 1806-1822, 1825, 1830-1833, 1834-1856, 1863, 1864, 1869-1872, 1874, 1876, 1878, 1880, 1882, 1884-1890, 1901-1909, 1913, 1917, 1921, 1925-1930, 1932, 1934, 1937, 1940, 1942-1973, 2004, 2005-2011, 2012-2033, 2041-2050, 2094, 2095, 2102-2104, 2106, 2108, 2110, 2112, 2114, 2116, and 2119-2157;   (c) sequences having at least 90% identity to the amino acid sequence as provided in SEQ ID NO:324-340, 783, 786, 787, 789, 791, 793, 795, 797-799, 805, 806, 809, 827, 1667, 1670-1675, 1677-1679, 1806-1822, 1825, 1830-1833, 1834-1856, 1863, 1864, 1869-1872, 1874, 1876, 1878, 1880, 1882, 1884-1890, 1901-1909, 1913, 1917, 1921, 1925-1930, 1932, 1934, 1937, 1940, 1942-1973, 2004, 2005-2011, 2012-2033, 2041-2050, 2094, 2095, 2102-2104, 2106, 2108, 2110, 2112, 2114, 2116, and 2119-2157;   (d) sequences consisting of at least 10, 20, 25, 30, 35, 40, 45, 50, 75 and 100 contiguous residues of a sequence provided in SEQ ID NO: 324-340, 783, 786, 787, 789, 791, 793, 795, 797-799, 805, 806, 809, 827, 1667, 1670-1675, 1677-1679, 1806-1822, 1825, 1830-1833, 1834-1856, 1863, 1864, 1869-1872, 1874, 1876, 1878, 1880, 1882, 1884-1890, 1901-1909, 1913, 1917, 1921, 1925-1930, 1932, 1934, 1937, 1940, 1942-1973, 2004, 2005-2011, 2012-2033, 2041-2050, 2094, 2095, 2102-2104, 2106, 2108, 2110, 2112, 2114, 2116, and 2119-2157;   (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 .   
     
     
         3 . An expression vector comprising a polynucleotide of  claim 1  or a polynucleotide which encodes a polypeptide of  claim 2  operably linked to an expression control sequence. 
     
     
         4 . A host cell transformed or transfected with an expression vector according to  claim 3 . 
     
     
         5 . An isolated antibody, or antigen-binding fragment thereof, that specifically binds to a polypeptide according to  claim 2 . 
     
     
         6 . An isolated antibody or antigen-binding fragment thereof according to  claim 5 , wherein the polypeptide is provided in SEQ ID NO:324-340, 783, 786, 787, 789, 791, 793, 795, 797-799, 805, 806, 809, 827, 1667, 1670-1675, 1677-1679, 1806-1822, 1825, 1830-1833, 1834-1856, 1863, 1864, 1869-1872, 1874, 1876, 1878, 1880, 1882, 1884-1890, 1901-1909, 1913, 1917, 1921, 1925-1930, 1932, 1934, 1937, 1940, 1942-1973, 2004, 2005-2011, 2012-2033, 2041-2050, 2094, 2095, 2102-2104, 2106, 2108, 2110, 2112, 2114, 2116, and 2119-2157. 
     
     
         7 . 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 of  claim 2 ;   (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 or a control value and therefrom determining the presence or absence of a cancer in the patient.   
     
     
         8 . A fusion protein comprising a polypeptide of  claim 2 . 
     
     
         9 . The fusion protein according to  claim 8 , wherein the at least one polypeptide consists of at least 20 contiguous amino acid residues of a polypeptide set forth in: SEQ ID NO:324-340, 783, 786, 787, 789, 791, 793, 795, 797-799, 805, 806, 809, 827, 1667, 1670-1675, 1677-1679, 1806-1822, 1825, 1830-1833, 1834-1856, 1863, 1864, 1869-1872, 1874, 1876, 1878, 1880, 1882, 1884-1890, 1901-1909, 1913, 1917, 1921, 1925-1930, 1932, 1934, 1937, 1940, 1942-1973, 2004, 2005-2011, 2012-2033, 2041-2050, 2094, 2095, 2102-2104, 2106, 2108, 2110, 2112, 2114, 2116, and 2119-2157. 
     
     
         10 . An oligonucleotide that hybridizes to a sequence set forth in  claim 1  under highly stringent conditions. 
     
     
         11 . 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 according to  claim 2 ;   (b) a polynucleotide that encodes a polypeptide according to  claim 2 ;   (c) sequences that hybridize to a polynucleotide according to (b) under highly stringent conditions;   (d) antigen-presenting cells that express a polypeptide according to (a),   under conditions and for a time sufficient to permit the stimulation and/or expansion of T cells.   
     
     
         12 . An isolated T cell population, comprising T cells prepared according to the method of  claim 11 . 
     
     
         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 2 ;   (b) a polynucleotide according to  claim 1 ;   (c) sequences that hybridize to a polynucleotide according to  claim 1  under highly stringent conditions;   (d) antibodies according to  claim 5 ;   (e) fusion proteins according to  claim 8 ;   (f) T cell populations according to  claim 12 ; and   (g) antigen presenting cells that express a polypeptide or fusion protein according to (a) or (e).   
     
     
         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 10 ;   (c) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; and   (d) comparing the amount of polynucleotide that hybridizes to the oligonucleotide to a predetermined cut-off value or a control value, and therefrom determining the presence or absence of the cancer in the patient.   
     
     
         17 . A diagnostic kit comprising at least one oligonucleotide according to  claim 10 . 
     
     
         18 . A diagnostic kit comprising at least one antibody according to  claim 5  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 2 ; 
 (ii) polynucleotides according to  claim 1 , 
 (iii) a polynucleotide which encodes a polypeptide according to  claim 2 , 
 (iv) sequences that hybridize to a polynucleotide according to  claim 1 , under highly stringent conditions, 
 (v) antigen presenting cells that express a polypeptide according to (i) or (iii), 
 (vi) 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.