Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library

  • Yao-Tseng Chen
    Cornell University Medical College and Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan–Kettering Cancer Center, New York, NY 10021; and Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, 60488 Frankfurt, Germany
  • Ali O. Güre
    Cornell University Medical College and Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan–Kettering Cancer Center, New York, NY 10021; and Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, 60488 Frankfurt, Germany
  • Solam Tsang
    Cornell University Medical College and Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan–Kettering Cancer Center, New York, NY 10021; and Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, 60488 Frankfurt, Germany
  • Elisabeth Stockert
    Cornell University Medical College and Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan–Kettering Cancer Center, New York, NY 10021; and Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, 60488 Frankfurt, Germany
  • Elke Jäger
    Cornell University Medical College and Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan–Kettering Cancer Center, New York, NY 10021; and Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, 60488 Frankfurt, Germany
  • Alexander Knuth
    Cornell University Medical College and Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan–Kettering Cancer Center, New York, NY 10021; and Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, 60488 Frankfurt, Germany
  • Lloyd J. Old
    Cornell University Medical College and Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan–Kettering Cancer Center, New York, NY 10021; and Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, 60488 Frankfurt, Germany

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<jats:p>Cancer/testis (CT) antigens—immunogenic protein antigens that are expressed in testis and a proportion of diverse human cancer types—are promising targets for cancer vaccines. To identify new CT antigens, we constructed an expression cDNA library from a melanoma cell line that expresses a wide range of CT antigens and screened the library with an allogeneic melanoma patient serum known to contain antibodies against two CT antigens, MAGE-1 and NY-ESO-1. cDNA clones isolated from this library identified four CT antigen genes: MAGE-4a, NY-ESO-1, LAGE-1, and CT7. Of these four, only MAGE-4a and NY-ESO-1 proteins had been shown to be immunogenic. LAGE-1 is a member of the NY-ESO-1 gene family, and CT7 is a newly defined gene with partial sequence homology to the MAGE family at its carboxyl terminus. The predicted CT7 protein, however, contains a distinct repetitive sequence at the 5′ end and is much larger than MAGE proteins. Our findings document the immunogenicity of LAGE-1 and CT7 and emphasize the power of serological analysis of cDNA expression libraries in identifying new human tumor antigens.</jats:p>

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