Abstract
The presence of tumor infiltrating T cells has been shown to be associated with a favorable prognosis in different tumor types. Several strategies have been developed to identify relevant tumor antigens which can be used for active immunotherapy strategies. The SEREX technique (serological analysis of cDNA expression libraries) identifies tumor antigens based on a spontaneous humoral immune response in cancer patients. This technique is not limited to tumor types that can be grown in cell culture or depends on established T cell clones recognizing the autologous tumor. Several steps of analysis are mandatory to evaluate SEREX-defined antigens before they become new target antigens for active immunotherapy: expression analysis; serological analysis with sera from tumor patients and normal individuals; identification of potential peptide epitopes for CD8 T cells and evaluation in T cell assays. This article summarizes our approach of antigen identification and evaluation giving the example of the recently cloned breast cancer antigen NY-BR-1.
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Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, Ohtani H (1998) CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 58:3491–3494
Nakano O, Sato M, Naito Y, Suzuki K, Orikasa S, Aizawa M, Suzuki Y, Shintaku I, Nagura H, Ohtani H (2001) Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res 61:5132–5136
Schumacher K, Haensch W, Roefzaad C, Schlag PM (2001) Prognostic significance of activated CD8(+) T cell infiltrations within esophageal carcinomas. Cancer Res 61:3932–3936
Eerola AK, Soini Y, Paakko P (2000) A high number of tumor-infiltrating lymphocytes are associated with a small tumor size, low tumor stage, and a favorable prognosis in operated small cell lung carcinoma. Clin Cancer Res 6:1875–1881
van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254:1643–1647
Boel P, Wildmann C, Sensi ML, Brasseur R, Renauld JC, Coulie P, Boon T, van der Bruggen P (1995) BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity 2:167–175
Van den Eynde B, Peeters O, De Backer O, Gaugler B, Lucas S, Boon T (1995) A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med 182:689–698
Boon T, van der Bruggen P (1996) Human tumor antigens recognized by T lymphocytes. J Exp Med 183:725–729
Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT (2002) Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev 188:22–32
Coulie PG, Brichard V, Van Pel A, Wolfel T, Schneider J, Traversari C, Mattei S, De Plaen E, Lurquin C, Szikora JP et al (1994) A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas [see comments]. J Exp Med 180:35–42
Brichard V, Van Pel A, Wolfel T, Wolfel C, De Plaen E, Lethe B, Coulie P, Boon T (1993) The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 178:489–495
Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Sakaguchi K, Appella E, Yannelli JR, Adema GJ, Miki T, Rosenberg SA (1994) Identification of a human melanoma antigen recognized by tumor- infiltrating lymphocytes associated with in vivo tumor rejection. Proc Natl Acad Sci U S A 91:6458–6462
Wang RF, Robbins PF, Kawakami Y, Kang XQ, Rosenberg SA (1995) Identification of a gene encoding a melanoma tumor antigen recognized by HLA-A31-restricted tumor-infiltrating lymphocytes [published erratum appears in J Exp Med (1995) 181(3):1261]. J Exp Med 181:799–804
Wolfel T, Hauer M, Schneider J, Serrano M, Wolfel C, Klehmann-Hieb E, De Plaen E, Hankeln T, Meyer zum Buschenfelde KH, Beach D (1995) A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 269:1281–1284
Gnjatic S, Cai Z, Viguier M, Chouaib S, Guillet JG, Choppin J (1998) Accumulation of the p53 protein allows recognition by human CTL of a wild-type p53 epitope presented by breast carcinomas and melanomas. J Immunol 160:328–333
Jochmus I, Osen W, Altmann A, Buck G, Hofmann B, Schneider A, Gissmann L, Rammensee HG (1997) Specificity of human cytotoxic T lymphocytes induced by a human papillomavirus type 16 E7-derived peptide. J Gen Virol 78(7):1689–1695
Rammensee HG, Weinschenk T, Gouttefangeas C, Stevanovic S (2002) Towards patient-specific tumor antigen selection for vaccination. Immunol Rev 188:164–176
Jager E, Jager D, Knuth A (2002) Clinical cancer vaccine trials. Curr Opin Immunol 14:178–182
Jager E, Nagata Y, Gnjatic S, Wada H, Stockert E, Karbach J, Dunbar PR, Lee SY, Jungbluth A, Jager D, Arand M, Ritter G, Cerundolo V, Dupont B, Chen YT, Old LJ, Knuth A (2000) Monitoring CD8 T cell responses to NY-ESO-1: correlation of humoral and cellular immune responses. Proc Natl Acad Sci U S A 97:4760–4765
Jaeger E, Bernhard H, Romero P, Ringhoffer M, Arand M, Karbach J, Ilsemann C, Hagedorn M, Knuth A (1996) Generation of cytotoxic T-cell responses with synthetic melanoma-associated peptides in vivo: implications for tumor vaccines with melanoma-associated antigens. Int J Cancer 66:162–169
Jager E, Chen YT, Drijfhout JW, Karbach J, Ringhoffer M, Jager D, Arand M, Wada H, Noguchi Y, Stockert E, Old LJ, Knuth A (1998) Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1: definition of human histocompatibility leukocyte antigen (HLA)-A2-binding peptide epitopes. J Exp Med 187:265–270
Jager E, Gnjatic S, Nagata Y, Stockert E, Jager D, Karbach J, Neumann A, Rieckenberg J, Chen YT, Ritter G, Hoffman E, Arand M, Old LJ, Knuth A (2000) Induction of primary NY-ESO-1 immunity: CD8+ T lymphocyte and antibody responses in peptide-vaccinated patients with NY-ESO-1+ cancers. Proc Natl Acad Sci U S A 97:12198–12203
Jager E, Ringhoffer M, Dienes HP, Arand M, Karbach J, Jager D, Ilsemann C, Hagedorn M, Oesch F, Knuth A (1996) Granulocyte-macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo. Int J Cancer 67:54–62
Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Restifo NP, Dudley ME, Schwarz SL, Spiess PJ, Wunderlich JR, Parkhurst MR, Kawakami Y, Seipp CA, Einhorn JH, White DE (1998) Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma [see comments]. Nat Med 4:321–327
Marchand M, van Baren N, Weynants P, Brichard V, Dreno B, Tessier MH, Rankin E, Parmiani G, Arienti F, Humblet Y, Bourlond A, Vanwijck R, Lienard D, Beauduin M, Dietrich PY, Russo V, Kerger J, Masucci G, Jager E, De Greve J, Atzpodien J, Brasseur F, Coulie PG, van der Bruggen P, Boon T (1999) Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int J Cancer 80:219–230
Sahin U, Tureci O, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfreundschuh M (1995) Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A 92:11810–11813
Scanlan MJ, Gout I, Gordon CM, Williamson B, Stockert E, Gure AO, Jäger D, Chen Y-T, Mackay A, O’Hare MJ, Old LJ (2001) Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression. Cancer Immun 1:4
Ayyoub M, Stevanovic S, Sahin U, Guillaume P, Servis C, Rimoldi D, Valmori D, Romero P, Cerottini JC, Rammensee HG, Pfreundschuh M, Speiser D, Levy F (2002) Proteasome-assisted identification of a SSX-2-derived epitope recognized by tumor-reactive CTL infiltrating metastatic melanoma. J Immunol 168:1717–1722
Tureci O, Chen YT, Sahin U, Gure AO, Zwick C, Villena C, Tsang S, Seitz G, Old LJ, Pfreundschuh M (1998) Expression of SSX genes in human tumors. Int J Cancer 77:19–23
Chen YT, Scanlan MJ, Sahin U, Tureci O, Gure AO, Tsang S, Williamson B, Stockert E, Pfreundschuh M, Old LJ (1997) A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci U S A 94:1914–1918
Chen YT, Gure AO, Tsang S, Stockert E, Jager E, Knuth A, Old LJ (1998) Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library. Proc Natl Acad Sci U S A 95:6919–6923
Tureci O, Sahin U, Zwick C, Koslowski M, Seitz G, Pfreundschuh M (1998) Identification of a meiosis-specific protein as a member of the class of cancer/testis antigens. Proc Natl Acad Sci U S A 95:5211–5216
Eichmuller S, Usener D, Dummer R, Stein A, Thiel D, Schadendorf D (2001) Serological detection of cutaneous T-cell lymphoma-associated antigens. Proc Natl Acad Sci U S A 98:629–634
Ono T, Kurashige T, Harada N, Noguchi Y, Saika T, Niikawa N, Aoe M, Nakamura S, Higashi T, Hiraki A, Wada H, Kumon H, Old LJ, Nakayama E (2001) Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen. Proc Natl Acad Sci U S A 98:3282–3287
Tureci O, Sahin U, Koslowski M, Buss B, Bell C, Ballweber P, Zwick C, Eberle T, Zuber M, Villena-Heinsen C, Seitz G, Pfreundschuh M (2002) A novel tumour associated leucine zipper protein targeting to sites of gene transcription and splicing. Oncogene 21:3879–3888
Cho B, Lim Y, Lee DY, Park SY, Lee H, Kim WH, Yang H, Bang YJ, Jeoung DI (2002) Identification and characterization of a novel cancer/testis antigen gene CAGE. Biochem Biophys Res Commun 292:715–726
Lee SY, Obata Y, Yoshida M, Stockert E, Williamson B, Jungbluth AA, Chen YT, Old LJ, Scanlan MJ (2003) Immunomic analysis of human sarcoma. Proc Natl Acad Sci U S A 100:2651–2656
Jager D, Stockert E, Jager E, Gure AO, Scanlan MJ, Knuth A, Old LJ, Chen YT (2000) Serological cloning of a melanocyte rab guanosine 5’-triphosphate-binding protein and a chromosome condensation protein from a melanoma complementary DNA library. Cancer Res 60:3584–3591
Jager D, Stockert E, Gure AO, Scanlan MJ, Karbach J, Jager E, Knuth A, Old LJ, Chen YT (2001) Identification of a tissue-specific putative transcription factor in breast tissue by serological screening of a breast cancer library. Cancer Res 61:2055–2061
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This work was presented at the first Cancer Immunology and Immunotherapy Summer School, 8–13 September 2003, Ionian Village, Bartholomeio, Peloponnese, Greece.
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Jäger, D., Taverna, C., Zippelius, A. et al. Identification of tumor antigens as potential target antigens for immunotherapy by serological expression cloning. Cancer Immunol Immunother 53, 144–147 (2004). https://doi.org/10.1007/s00262-003-0470-z
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DOI: https://doi.org/10.1007/s00262-003-0470-z