Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Review of Cancer-Testis (CT) Genes

Cancer-testis (CT) 유전자의 고찰

  • Kim, Mi-Hee (Department of Biochemistry, School of Medicine, Pusan national University) ;
  • Song, Myung-Ha (Department of Biochemistry, School of Medicine, Pusan national University) ;
  • Lee, Sang-Yull (Department of Biochemistry, School of Medicine, Pusan national University)
  • 김미희 (부산대학교 의학전문대학원 생화학교실) ;
  • 송명하 (부산대학교 의학전문대학원 생화학교실) ;
  • 이상률 (부산대학교 의학전문대학원 생화학교실)
  • Received : 2011.05.19
  • Accepted : 2011.06.20
  • Published : 2011.06.30
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Abstract

Cancer-testis (CT) antigens are immunogenic protein antigens with restricted expression in the testes and a wide range of human tumor types, eliciting both humoral and cellular immune responses in cancer patients. They are considered to be ideal targets for vaccine-based immunotherapy, and more than 100 CT antigens, including MAGE, NY-ESO-1, GAGE, BAGE, LAGE, SSX2 and NY-SAR-35 have been identified to date. The CT antigens were identified through various techniques and can be divided in those that are encoded on the X chromosome, the CT-X genes, and those that are not, the non-X-CT genes. CT genes are aberrantly activated and expressed in a proportion of various types of human cancers. The biological role of CT-X in both germ line tissues and tumors remains poorly understood. Cancer vaccine trials based on several CT antigens are currently ongoing. This paper reviews recent advances in and future trends of CT antigens for cancer immunotherapy.

Cancer-testis (CT) antigen은 다양한 종양과 정상 고환에서 제한적으로 발현되고, 암환자에서 체액성 면역과 세포성 면역반응을 일으키는 종양항원이다. 지금까지 MAGE, NY-ESO-1, GAGE, BAGE, LAGE, SSX2, NY-SAR-35를 포함하여 100개 이상의 CT antigen들이 동정되었고, 이러한 CT antigen들은 백신을 이용한 면역치료에 있어서 중요한 요소로 작용할 것으로 사료된다. CT antigen은 여러 가지 방법들을 통해 확인할 수 있고, X 염색체에 암호화 되어있는 CT-X gene과 X 염색체에 암호화 되어있지 않은 non-X CT gene으로 나눌 수 있다. 또한 몇몇의 종양에서 비정상적으로 활성화되지 않거나 발현되지 않는 CT antigen도 존재한다. 생식세포 조직과 종양에서 CT-X gene의 생물학적 역할이 아직 명확하게 규명되지 않았지만, 현재 여러 종류의 CT antigen을 이용한 암백신 치료법이 시도되고 있다. 본 논문은 암의 면역치료를 위한 CT antigen의 최근 연구동향과 앞으로의 연구방향에 대해 서술하고자 한다.

Keywords

References

  1. Akers, S. N., K. Odunsi, and A. R. Karpf. 2010. Regulation of cancer germline antigen gene expression: implications for cancer immunotherapy. Future Oncol. 6, 717-732. https://doi.org/10.2217/fon.10.36
  2. Bai, S., B. He, and E. M. Wilson. 2005. Melanoma antigen gene protein MAGE-11 regulates androgen receptor function by modulating the interdomain interaction. Mol. Cell Biol. 25, 1238-1257. https://doi.org/10.1128/MCB.25.4.1238-1257.2005
  3. Boel, P., C. Wildmann, M. L. Sensi, R. Brasseur, J. C. Renauld, P. Coulie, T. Boon, and P. van der Bruggen. 1995. BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity 2, 167-175. https://doi.org/10.1016/S1074-7613(95)80053-0
  4. Caballero, O. L. and Y. T. Chen. 2009. Cancer⁄testis (CT) antigens: Potential targets for immunotherapy. Cancer Sci. 100, 2014-2021. https://doi.org/10.1111/j.1349-7006.2009.01303.x
  5. Chen, Y. T., A. O. Gure, S. Tsang, E. Stockert, E. Jager, A. Knuth, and L. J. Old. 1998. Identification of multiple cancer⁄testis antigens by allogeneic antibody screening of a melanoma cell line library. Proc. Natl. Acad. Sci. USA 95, 6919-6923. https://doi.org/10.1073/pnas.95.12.6919
  6. Chen, Y. T., M. J. Scanlan, U. Sahin, O. Türeci, A. O. Gure, S. Tsang, B. Williamson, E. Stockert, M. Pfreundschuh, and L. J. Old. 1997. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc. Natl. Acad. Sci. USA 94, 1914-1918. https://doi.org/10.1073/pnas.94.5.1914
  7. Chen, Y. T., M. J. Scanlan, C. A. Venditti, R. Chua, G. Theiler, B. J. Stevenson, C. Iseli, A. O. Gure, T. Vasicek, R. L. Strausberg, C. V. Jongeneel, L. J. Old, and A. J. Simpson. 2005. Identification of cancer⁄testis antigen genes by massively parallel signature sequencing. Proc. Natl. Acad. Sci. USA 102, 7940-7945. https://doi.org/10.1073/pnas.0502583102
  8. Chomez, P., O. De Backer, M. Bertrand, E. De Plaen, T. Boon, and S. Lucas. 2001. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res. 61, 5544-5551.
  9. Duan, Z., Y. Duan, D. E. Lamendola, R. Z. Yusuf, R. Naeem, R. T. Penson, and M. V. Seiden. 2003. Overexpression of MAGE/GAGE genes in paclitaxel/doxorubicin-resistant human cancer cell lines. Clin. Cancer Res. 9, 2778-2785.
  10. Fratta, E., S. Coral, A. Covre, G. Parisi, F. Colizzi, R. Danielli, H. J. Marie Nicolay, L. Sigalotti, and M. Maio. 2011. The biology of cancer testis antigens: Putative function, regulation and therapeutic potential. Mol. Oncol. 5, 164-182 https://doi.org/10.1016/j.molonc.2011.02.001
  11. Gaugler, B., B. Van den Eynde, P. van der Bruggen, P. Romero, J. J. Gaforio, E. De Plaen, B. Lethé, F. Brasseur, and T. Boon. 1994. Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes. J. Exp. Med. 179, 921-930. https://doi.org/10.1084/jem.179.3.921
  12. Ghafouri-Fard, S. and M. H. Modarressi. 2009. Cancer-testis antigens: potential targets for canceri. Arch. Iran. Med. 12, 395-404.
  13. Gure, A. O., E. Stockert, K. C. Arden, A. D. Boyer, C. S. Viars, M. J. Scanlan, L. J. Old, and Y. T. Chen. 2000. CT10: a new cancer-testis (CT) antigen homologous to CT7 and the MAGE family, identified by representationaldifference analysis. Int. J. Cancer 85, 726-732. https://doi.org/10.1002/(SICI)1097-0215(20000301)85:5<726::AID-IJC21>3.0.CO;2-F
  14. Harada, N., K. Hoshiai, Y. Takahashi, Y. Sakaguchi, T. Kuno, T. shida, and H. Shiku. 2008. Preclinical safety pharmacology study of a novel protein-based cancer vaccine CHP-NY-ESO-1. Kobe. J. Med. Sci. 54, E23-34.
  15. Jager, E., J. Karbach, S. Gnjatic, A. Neumann, A. Bender, D. Valmori, M. Ayyoub, E. Ritter, G. Ritter, D. Jäger, D. Panicali, E. Hoffman, L. Pan, H. Oettgen, L. J. Old, and A. Knuth. 2006. Recombinant vaccinia ⁄ fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients. Proc. Natl. Acad. Sci. USA 103, 14453-14458. https://doi.org/10.1073/pnas.0606512103
  16. Jungbluth, A. A., W. A. Silva Jr, K. Iversen, D. Frosina, B. Zaidi, K. Coplan, S. K. Eastlake-Wade, S. B. Castelli, G. C. Spagnoli, L. J. Old, and M. Vogel. 2007. Expression of cancer- testis (CT) antigens in placenta. Cancer Immun. 7, 15-29.
  17. Kaneda, A., T. Tsukamoto, T. Takamura-Enya, N. Watanabe, M. Kaminishi, T. Sugimura, M. Tatematsu, and T. Ushijima. 2004. Frequent hypomethylation in multiple promoter CpG islands is associated with global hypomethylation, but not with frequent promoter hypermethylation. Cancer Sci. 95, 58-64. https://doi.org/10.1111/j.1349-7006.2004.tb03171.x
  18. Lee, S. Y. 2007. SEREX: discovery of tumor antigens. J. Life Sci. 17, 841-846. https://doi.org/10.5352/JLS.2007.17.6.841
  19. Lee, S. Y., Y. Obata, M. Yoshida, E. Stockert, B. Williamson, A. A. Jungbluth, Y. T. Chen, L. J. Old, and M. J. Scanlan. 2003. Immunomic analysis of human sarcoma. Proc. Natl. Acad. Sci. USA 100, 2651-2656. https://doi.org/10.1073/pnas.0437972100
  20. Lehmann, F, L. J., S. Gaulis, O. Gruselle, and V. Brichard. 2008. Clinical response to the MAGE-A3 immunotherapeutic in metastatic melanoma patients is associated with a specific gene profile present prior to treatment. XVIth meeting in the cancer research institute international cancer immunotherapy symposium series and the 2008 meeting of the cancer vaccine consortium. New York City. S25.
  21. Madsen, B., M. Tarsounas, J. M. Burchell, D. Hall, R. Poulsom, and J. Taylor-Papadimitriou. 2003. PLU-1, a transcriptional repressor and putative testis-cancer antigen, has a specific expression and localisation pattern during meiosis. Chromosoma 112, 124-132. https://doi.org/10.1007/s00412-003-0252-6
  22. Manning, A. T., J. T. Garvin, R. I. Shahbazi, N. Miller, R. E. McNeill, and M. J. Kerin. 2007. Molecular profiling techniques and bioinformatics in cancer research. Eur. J. Surg. Oncol. 33, 255-265. https://doi.org/10.1016/j.ejso.2006.09.002
  23. Marchand, M., N. van Baren, P. Weynants, V. Brichard, B. Dréno, M. H. Tessier, E. Rankin, G. Parmiani, F. Arienti, Y. Humblet, A. Bourlond, R. Vanwijck, D. Liénard, M. Beauduin, P. Y. Dietrich, V. Russo, J. Kerger, G. Masucci, E. Jäger, J. De Greve, J. Atzpodien, F. Brasseur, P. G. Coulie, P. van der Bruggen, and T. Boon. 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. https://doi.org/10.1002/(SICI)1097-0215(19990118)80:2<219::AID-IJC10>3.0.CO;2-S
  24. Meklat, F., Z. Li, Z. Wang, Y. Zhang, J. Zhang, A. Jewell, and S. H. Lim. 2007. Cancer-testis antigens in haematological malignancies. Br. J. Haematol. 136, 769-776. https://doi.org/10.1111/j.1365-2141.2006.06484.x
  25. Mischo, A., B. Kubuschok, K. Ertan, K. Preuss, B. Romeike, E. Regitz, E. Regitz, C. Schormann, D. de Bruijn, A. Wadle, F. Neumann, W. Schmidt, C. Renner, and M. Pfreundschuh. 2006. Prospective study on the expression of cancer testis genes and antibody responses in 100 consecutive patients with primary breast cancer. Int. J. Cancer 118, 696-703. https://doi.org/10.1002/ijc.21352
  26. Nagao, T., H. Higashitsuji, K. Nonoguchi, T. Sakurai, S. Dawson, R. J. Mayer, K. Itoh, and J. Fujita. 2003. MAGE-A4 interacts with the liver oncoprotein gankyrin and suppresses its tumorigenic activity. J. Biol. Chem. 278, 10668-10674. https://doi.org/10.1074/jbc.M206104200
  27. Nicholaou, T., L. M. Ebert, I. D. Davis, G. A. McArthur, H. Jackson, N. Dimopoulos, B. Tan, E. Maraskovsky, L. Miloradovic, W. Hopkins, L. Pan, R. Venhaus, E. W. Hoffman, W. Chen, and J. Cebon. 2009. Regulatory T-cell-mediated attenuation of T-cell responses to the NY-ESO-1 ISCOMATRIX vaccine inpatients with advanced malignant melanoma. Clin. Cancer Res. 15, 2166-2173. https://doi.org/10.1158/1078-0432.CCR-08-2484
  28. Old, L. J. and Y. T. Chen. 1998. New paths in human cancer serology. J. Exp. Med. 187, 1163-1167. https://doi.org/10.1084/jem.187.8.1163
  29. Ollinger, R., M. Alsheimer, and R. Benavente. 2005. Mammalian protein SCP1 forms synaptonemal complex-like structures in the absence of meiotic chromosomes. Mol. Biol. Cell 16, 212-217.
  30. Ross, M. T., D. V. Grafham, A. J. Coffey, S. Scherer, K. McLay, D. Muzny, and et al. 2005. The DNA sequence of the human X chromosome. Nature 434, 325-337. https://doi.org/10.1038/nature03440
  31. Sahin, U., O. Türeci, Y. T. Chen, G. Seitz, C. Villena-Heinsen, L. J. Old, and M. Pfreundschuh. 1998. Expression of multiple cancer/testis (CT) antigens in breast cancer and melanoma: basis for polyvalent CT vaccine strategies. Int. J. Cancer 78, 387-389. https://doi.org/10.1002/(SICI)1097-0215(19981029)78:3<387::AID-IJC22>3.0.CO;2-2
  32. Sahin, U., O. Tureci, and M. Pfreundschuh. 1997. Serological identification of human tumor antigens. Curr. Opin. Immunol. 9, 709-716. https://doi.org/10.1016/S0952-7915(97)80053-2
  33. Sahin, U., O. Tureci, H. Schmitt, B. Cochlovius, T. Johannes, R. Schmits, F. Stenner, G. Luo, I. Schobert, and M. Pfreundschuh. 1995. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc. Natl. Acad. Sci. USA 92, 11810-11813. https://doi.org/10.1073/pnas.92.25.11810
  34. Scanlan, M. J., A. O. Gure, A. A. Jungbluth, L. J. Old, and Y. T. Chen. 2002. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol. Rev. 188, 22-32. https://doi.org/10.1034/j.1600-065X.2002.18803.x
  35. Simpson, A. J., O. L. Caballero, A. Jungbluth, Y. T. Chen, and L. J. Old. 2005. Cancer-testis antigens, gametogenesis and cancer. Nat. Rev. Cancer 5, 615-625. https://doi.org/10.1038/nrc1669
  36. Sugita, M., M. Geraci, B. Gao, R. L. Powell, F. R. Hirsch, G. Johnson, R. Lapadat, E. Gabrielson, R. Bremnes, P. A. Bunn, and W. A. Franklin. 2002. Combined use of oligonucleotide and tissue microarrays identifies cancer/testis antigens as biomarkers in lung carcinoma. Cancer Res. 62, 3971-3979.
  37. Tajima, K., Y. Obata, H. Tamaki, M. Yoshida, Y. T. Chen, M. J. Scanlan, L. J. Old, H. Kuwano, T. Takahashi, T. Takahashi, and T. Mitsudomi. 2003. Expression of cancer/ testis (CT) antigens in lung cancer. Lung Cancer 42, 23-33. https://doi.org/10.1016/S0169-5002(03)00244-7
  38. Tanaka, R., T. Ono, S. Sato, T. Nakada, F. Koizumi, K. Hasegawa, K. Nakagawa, H. Okumura, T. Yamashita, M. Ohtsuka, K. Asagoe, O. Yamasaki, Y. Noguchi, K. Iwatsuki, and E. Nakayama. 2004. Over-expressin of the testis-specific gene TSGA10 in cancers and its immunogenicity. Microbiol. Immunol. 48, 339-345. https://doi.org/10.1111/j.1348-0421.2004.tb03515.x
  39. Van den Eynde, B., O. Peeters, O. De Backer, B. Gaugler, S. Lucas, and T. Boon. 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. https://doi.org/10.1084/jem.182.3.689
  40. Van der Bruggen, P., C. Traversari, P. Chomez, C. Lurquin, E. De Plaen, B. Van den Eynde, A. Knuth, and T. Boon. 1991. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254, 1643-1647. https://doi.org/10.1126/science.1840703
  41. Van Pel, A., P. van der Bruggen, P. G. Coulie, V. G. Brichard, B. Lethé, B. van den Eynde, C. Uyttenhove, J. C. Renauld, and T. Boon. 1995. Genes coding for tumour antigens recognized by cytolytic T lymphocytes. Immunol. Rev. 145, 229-250. https://doi.org/10.1111/j.1600-065X.1995.tb00084.x
  42. Wadle, A., B. Kubuschok, J. Imig, B. Wuellner, C. Wittig, C. Zwick, A. Mischo, K. Waetzig, B. Romeike, W. Lindemann, M. Schilling, M. Pfreundschuh, and C. Renner. 2006. Serological immune responses to cancer testis antigens in patients with pancreatic cancer. Int. J. Cancer 119, 117-125. https://doi.org/10.1002/ijc.21744
  43. Yokoe, T., F. Tanaka, K. Mimori, H. Inoue, T. Ohmachi, M. Kusunoki, and M. Mori. 2008. Efficient identification of a novel cancer/testis antigen for immunotherapy using three-step microarray analysis. Cancer Res. 68, 1074-1082. https://doi.org/10.1158/0008-5472.CAN-07-0964
  44. Yuan, J., S. Gnjatic, H. Li, S. Powel, H. F. Gallardo, E. Ritter, G. Y. Ku, A. A. Jungbluth, N. H. Segal, T. S. Rasalan, G. Manukian, Y. Xu, R. A. Roman, S. L. Terzulli, M. Heywood, E. Pogoriler, G. Ritter, L. J. Old, J. P. Allison, and J. D. Wolchok. 2008. CTLA-4 blockade enhances polyfunctional NYESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit. Proc. Natl. Acad. Sci. USA 105, 20410-20415. https://doi.org/10.1073/pnas.0810114105