'1-8 interferon inducible gene family': putative colon carcinoma-associated antigens

• Published in: British journal of cancer Vol. 97; no. 12; pp. 1655 - 1663
• Main Authors: Tirosh, B, Daniel-Carmi, V, Carmon, L, Paz, A, Lugassy, G, Vadai, E, Machlenkin, A, Bar-Haim, E, Do, M-S, Ahn, I S, Fridkin, M, Tzehoval, E, Eisenbach, L
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 17-12-2007
• Subjects: Animals; Antibiotics; Antigens; Antigens, Tumor-Associated, Carbohydrate; Cancer research; Cell Line, Tumor; Colonic Neoplasms - genetics; Colonic Neoplasms - immunology; Colorectal cancer; Cross Reactions; Cytotoxicity; Genes; Humans; Immunodominant Epitopes; Immunology; Interferon; Interferons - chemistry; Interferons - pharmacology; Laboratory animals; Lymphocytes; Medical research; Membrane Proteins - genetics; Membrane Proteins - immunology; Mice; Mice, Transgenic; Peptides; Peptides - pharmacology; Science; T-Lymphocytes, Cytotoxic - immunology; Translational Therapeutics; Tumors; Israel
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604061

D(b-/-)xbeta2 microglobulin (beta2m) null mice transgenic for a chimeric HLA-A2.1/D(b)-beta2m single chain (HHD mice) are an effective biological tool to evaluate the antitumour cytotoxic T-lymphocyte response of known major histocompatibility-restricted peptide tumour-associated antigens, and to screen for putative unknown novel peptides. We utilised HHD lymphocytes to identify immunodominant epitopes of colon carcinoma overexpressed genes. We screened with HHD-derived lymphocytes over 500 HLA-A2.1-restricted peptides derived from colon carcinoma overexpressed genes. This procedure culminated in the identification of seven immunogenic peptides, three of these were derived from the 'human 1-8D gene from interferon inducible gene' (1-8D). The 1-8D gene was shown to be overexpressed in fresh tumour samples. The three 1-8D peptides were both antigenic and immunogenic in the HHD mice. The peptides induce cytotoxic T lymphocytes that were able to kill a colon carcinoma cell line HCT/HHD, in vitro and retard its growth in vivo. One of the peptides shared by all the 1-8 gene family primed efficiently normal human cytotoxic T lymphocyte precursors. These results highlight the 1-8D gene and its homologues as putative immunodominant tumour-associated antigens of colon carcinoma.