elevance of tumor-related/specific autoantibodies in patients` sera <strong>and</strong> of antigen expression in tumors, as well as the correlation with CTL responses <strong>and</strong> specific T helper cells. Well-designed clinical trials will answer the question whether our increased knowledge about these antigens can be translated into immuno- <strong>and</strong> gene therapeutic strategies with an improved prognosis for patients with malignant disease not curable <strong>by</strong> current st<strong>and</strong>ard therapy. Finally, the knowledge of the functional role of cancer-associated antigens provides us with a more profound insight into genetic <strong>and</strong> molecular alterations that play a role in the pathogenesis <strong>and</strong> growth of cancer. References 1 Maloney, D. G., Grillo, L. A.,White, C. A., Bodkin, D., Schilder, R. J., Neidhart, J. A., et al. (1997) IDEC- C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood, 90, 2188±2195. 2 Old, L. J. (1981) <strong>Cancer</strong> immunology: the search for specificity. G. H. A. Clowes Memorial lecture. <strong>Cancer</strong> Res., 41, 361±375. 3 van der Bruggen, P., Traversari, C., Chomez, P., Lurquin, C., De Plaen, E., van den Eynde, B., Knuth, A. <strong>and</strong> Boon, T. (1991) A gene encoding an antigen recognized <strong>by</strong> cytolytic T lymphocytes on a human melanoma. Science, 254, 1643±1647. 4 Sahin, U., Tçreci, Ú., Schmitt, H., Cochlovius, B., Johannes, T., Schmits, R., Stenner, F., Luo, G., Schobert, I. <strong>and</strong> Pfreundschuh, M. (1995) Human neoplasms elicit multiple immune responses in the autologous host. Proc. Natl Acad. Sci. USA, 92, 1180±11813. 5 Sahin, U., Tçreci, Ú. <strong>and</strong> Pfreundschuh, M. (1997) Serological identification of human tumor antigens. Curr. Opin. Immunol., 9, 709±716. 6 Tçreci, Ú., Sahin, U. <strong>and</strong> Pfreundschuh, M. (1997) Serological analysis of human tumor antigens: molecular definition <strong>and</strong> implications. Mol. Med. Today, 3, 342±349. 7 Tçreci, Ú., Sahin, U.,Vollmar, E., Siemer, S., Gættert, E., Seitz, G., Parkkila, A. K., Shah, G., Grubb, J. H., References Pfreundschuh, M. <strong>and</strong> Sly,W. S. (1998) Carbonic anhydrase XII: cDNA cloning, expression, <strong>and</strong> chromosomal localization of a novel carbonic anhydrase gene that is overexpressed in some renal cell cancers. Proc. Natl Acad. Sci. USA, 95, 7603±7613 8 Tçreci, Ú., Sahin, U., Schobert, I., Koslowski, M., Schmitt, H., Schild, H. J., Stenner, F., Seitz, G., Rammensee, H. G. <strong>and</strong> Pfreundschuh, M. (1996) The SSX2 gene, which is involved in the t(X,18) translocation of synovial sarcomas, codes for the human tumor antigen HOM-MEL-40. <strong>Cancer</strong> Res., 56, 4766±4772. 9 Chen,Y. T., Scanlan, J., Sahin, U., Tçreci, Ú., Gçre, A. O., Tsang, S., Williamson, S., Stockert, E., Pfreundschuh, M. <strong>and</strong> Old, L. J. (1997) A testicular antigen aberrantly expressed in human cancers detected <strong>by</strong> autologous antibody screening. Proc. Natl Acad. Sci. USA, 94, 1914±1918. 10 Tçreci, Ú., Sahin, U., Zwick, C., Koslowski, M., Seitz, G. <strong>and</strong> Pfreundschuh, M. (1998) Identification of a meiosis-specific protein as newmember of the cancer/testis antigen superfamily. Proc. Natl Acad. Sci. USA, 95, 5211±5216. 11 Brass, N., Heckel, D., Sahin, U., Pfreundschuh, M., Sybrecht, G. W. <strong>and</strong> Meese, E. (1997) Translation initiation factor eIF-4gamma is encoded <strong>by</strong> an amplified gene <strong>and</strong> induces an immune response in squamous cell lung carcinoma. Hum. Mol. Genet., 6, 33±39. 27
28 2 Serological Determinants On Tumor Cells 12 Boel, P.,Wildmann, C., Sensei, M. L., Brasseur, R., Renauld, M., Coulie, P., Boon, T. <strong>and</strong> van der Bruggen, P. (1995) BAGE: a newgene encoding an antigen recognized on human melanomas <strong>by</strong> cytolytic T lymphocytes. Immunity, 2, 167±175. 13 van den Eynde, B., Peeters, O., de Backer, O., Gaugler, B., Lucas, S. <strong>and</strong> Boon, T. (1995) A newfamily of genes coding for an antigen recognized <strong>by</strong> autologous cytolytic T lymphocytes on a human melanoma. J. Exp. Med., 182, 689±698. 14 Clark, J., Roques, J. P., Crew, J., Gill, S., Shipley, J., Ch<strong>and</strong>, A., Gusterson, B. <strong>and</strong> Cooper, C. S. (1994) Identification of novel genes SYT<strong>and</strong> SSX involved in the t(X,18)(p11.2,q11.2) translocation found in human synovial sarcoma. Nat. Genet., 7, 502±508. 15 Gçre, A. O., Tçreci, Ú., Sahin, U., Tsang, S., Scanlan, M., Jåger, E., Knuth, A., Preundschuh, M., Old, L. J. <strong>and</strong> Chen,Y. T. (1997). SSX, a multigene family with several members transcribed in normal testis <strong>and</strong> human cancer. Int. J. <strong>Cancer</strong>, 72, 965±971. 16 Tçreci, Ú., Chen,Y. T., Sahin, U., Gçre, A. O., Zwick, C.,Villena, C., Tsang, S., Seitz, G., Old, L. J. <strong>and</strong> Pfreundschuh, M. (1998) Expression of SSX genes in human tumors. Int. J. <strong>Cancer</strong>, 77, 19±23. 17 Lethe, B., Lucas, S., Michaux, L., De Smet, C., Godelaine, D., Serrano, A., De Plaen, E. <strong>and</strong> Boon, T. (1998) LAGE-1, a newgene with tumor specificity. Int. J. <strong>Cancer</strong>, 76, 903±908. 18 Jåger, E., Chen,Y. T., Drijfhout, J. W., Karbach, J., Ringhoffer, M., Jåger,D., Ar<strong>and</strong>, M.,Wada, H., Noguchi,Y., Stockert, E., Old. L. J. <strong>and</strong> Knuth A. (1998) Simultaneous humoral <strong>and</strong> 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. 19 Jåger, E., Stockert, E., Zidianakis, Z., Chen,Y. T., Karbach, J., Jager, D., Ar<strong>and</strong>, M., Ritter, G., Old, L. J. <strong>and</strong> Knuth, A. (1999) Humoral immune responses of cancer patients against ª<strong>Cancer</strong>-Testisº antigen NY-ESO-1: correlation with clinical events. Int. J. <strong>Cancer</strong>, 84, 506±10. 20 Stockert, E., Jåger, E., Chen,Y. T., Scanlan, M. J., Gout, I., Karbach, J., Ar<strong>and</strong>, M., Knuth, A. <strong>and</strong> Old, L. J. (1998) A survey of the humoral immune response of cancer patients to a panel of human tumor antigens. J. Exp. Med., 187, 1349±1354. 21 Schmits, R., Cochlovius, B., Treitz, G., Ketter, R., Preuss, K.-D., Romeike, B. F. M. <strong>and</strong> Pfreundschuh, M. (2001) Analysis of the antibody repertoire of astrocytoma patients against antigens expressed <strong>by</strong> gliomas. Int. J. <strong>Cancer</strong>, in press. nUpdate?n 22 Scanlan, M. J., Chen,Y. T., Williamson, B., Gçre, A. O., Stockert, E., Gordan, J. D., Tçreci, Ú., Sahin, U., Pfreundschuh, M. <strong>and</strong> Old, L. J. (1997) Characterization of human colon cancer antigens recognized <strong>by</strong> autologous antibodies. Int. J. <strong>Cancer</strong>, 76, 652± 658. 23 Pierre, P., Scheel, J., Rickard, J. E. <strong>and</strong> Kreis, T. (1992) CLIP-170 links endocytic vesicles to microtubules. Cell, 70, 887±892. 24 Stenner-Liewen, F., Luo, G., Sahin, U., Tçreci Ú., Koslowski, M, Kautz, I., Liewen, H. <strong>and</strong> Pfreundschuh, M. (2000) Definition of tumor-associated antigens in hepatocellular carcinoma. <strong>Cancer</strong> Epidemiol. Biomarkers Prevention, 9, 285±290. 25 Ivanov, S. V., Kuzmin, I.,Wei, M. H., Pack, S., Geil, L., Johnson, B. E., Stanbridge, E. J. <strong>and</strong> Lerman, M. I. (1998) Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines <strong>by</strong> wild-type von Hippel-Lindau transgenes. Proc. Natl Acad. Sci. USA, 95, 12596±601. 26 Parkkila, S., Rajaniemi, H., Parkkila, A. K., Kivela, J.,Waheed, A., Pastorekova, S., Pastorek, J. <strong>and</strong> Sly,W. S. (2000) Carbonic anhydrase inhibitor suppresses invasion of renal cancer cells in vitro. Proc. Natl Acad. Sci. USA, 97, 2220±2224. 27 Jåger, E., Jåger, D., Kargach, J., Chen,Y.-T., Ritter, G., Nagat,Y., Gnjatic, S., Stockert, E., Ar<strong>and</strong>, M., Old,
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Cancer Immune Therapie: Current and
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Editors: Dr. Gernot Stuhler Univers
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VI Preface Recent years have seen a
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VIII Contents 2.5.3 Antigens Encode
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X Contents 6.4.2 Natural Killer (NK
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268 Cancer Immune Therapie: Current
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380 Cancer Immune Therapie: Current
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384 Glossary suppressor gene produc
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386 Glossary press the proper recep
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392 Glossary T bodies are being tes