Serological detection of cutaneous T-cell lymphoma-associated antigens.
Cutaneous T-cell lymphomas (CTCL) are a group of skin neoplasms that originate from T lymphocytes and are difficult to treat in advanced stages. The present study is aimed at the identification of tumor-specific antigens from a human testis cDNA library using human sera known as the SEREX (serological identification of recombinantly expressed genes) approach. A cDNA library from normal testicle tissue was prepared and approximately 2 million recombinants were screened with sera from Sézary Syndrome and Mycosis fungoides patients. A total of 28 positive clones belonging to 15 different genes/ORFs were identified, including five hitherto unknown sequences. Whereas control sera did not react with most clones, 11-71% sera from CTCL patients were reactive against the identified clones. Expression analysis on 28 normal control and 17 CTCL tissues by reverse transcription-PCR (RT-PCR) and Northern blotting revealed seven ubiquitously distributed antigens, six differentially expressed antigens (several normal tissues were positive), and two tumor-specific antigens that were expressed only in testis and tumor tissues: (i) A SCP-1-like sequence, which has already been detected in various tumors, has been found in one CTCL tumor and four sera of CTCL patients reacted with various SCP-1-like clones and (ii) a new sequence named cTAGE-1 (CTCL-associated antigen 1) was detected in 35% of CTCL tumor tissues and sera of 6/18 patients reacted with this clone. The present study unravels CTCL-associated antigens independent of the T-cell receptor. The SCP-1-like gene and cTAGE-1 were shown to be immunogenic and immunologically tumor-specific and may therefore be candidates for immunotherapy targeting CTCL.
Eichmuller
S
S
German Cancer Research Center (DKFZ), Skin Cancer Unit (D0900), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Usener
D
D
Dummer
R
R
Stein
A
A
Thiel
D
D
Schadendorf
D
D
D000912:Antibodies, Neoplasm / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D015152:Blotting, Northern; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D005796:Genes; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009182:Mycosis Fungoides / Q000097:blood / Q000276:immunology*; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology; D016366:Open Reading Frames; D009928:Organ Specificity; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D012751:Sezary Syndrome / Q000097:blood / Q000276:immunology*; D012878:Skin Neoplasms / Q000097:blood / Q000276:immunology*; D013737:Testis / Q000378:metabolism
D000912:Antibodies, Neoplasm; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; C489753:SYCP1 protein, human