Cancer / testis antigen

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Cancer / Testis Antigen (in German Tumor / Testis Antigen ) refers to antigens that are formed by tumors and were originally identified in cancer .

properties

Cancer / Testis antigens are proteins and tumor antigens . They occur in tumors , briefly during embryogenesis and in healthy spermatocytes and are therefore a target antigen in the development of cancer vaccines and cancer immunotherapies with adoptive cell transfer . They are involved in meiosis in spermatocytes. Cancer / testis antigens result in the incomplete separation of chromosomes and aneuploidy , which is often observed in tumors . Many of the cancer / testis antigens are oncogenes and are involved in cellular processes such as cell growth and division , in the inhibition of apoptosis and in metastasis . They are therefore often involved in oncogenesis and malignant transformation .

The occurrence of cancer / testis antigen gene expression in tumors correlates with the progression of the tumor disease, which is why they also serve as biomarkers for the progression of a tumor disease. The immune privilege of spermatocytes avoids an immune reaction against healthy spermatocytes in the course of cancer immunotherapy. Spermatocytes do not have an MHCI and therefore can not activate cytotoxic T cells of the immune system. Due to the locally limited gene expression in healthy cells with immune privilege, there is less immune tolerance in the rest of the organism, despite the body's own origin of the proteins, which are used in cancer immunotherapy.

Types

Over 250 cancer / testis antigens have been described. They can be divided into twenty families or three groups ( Testis-Restricted , Testis / Brain-Restricted and Testis-Selective ). Examples are MAGE-A1 , MAGE-A3 , MAGE-C1 , BAGE , GAGE , HAGE , T21, SSX1 , SSX2 , SSX3 , SYCP-1 , PRAME , CT83 and NY-ESO-1 . The cancer / testis antigens on the X chromosome are predominantly only found in primates , while those on autosomes are evolutionarily conserved in many species . More than 10% of the genes on the X chromosome of primates are cancer / testis antigens.

Cancer / Testis Antigens are listed in the CTdatabase (formerly also at ACTAbase ).

history

In 1991 the first cancer / testis antigens MAGEA1, BAGE and GAGE ​​were identified by DNA sequencing of the genes of T cell receptors from cancer patients. SSX2, NY-ESO-1 and SYCP-1 were found in 1995 using SEREX .

literature

Individual evidence

  1. ^ FF Costa, K. Le Blanc, B. Brodin: Concise review: cancer / testis antigens, stem cells, and cancer. In: Stem cells (Dayton, Ohio). Volume 25, Number 3, March 2007, pp. 707-711, doi: 10.1634 / stemcells.2006-0469 , PMID 17138959 .
  2. ↑ a b c d e f F. de Carvalho, AL Vettore, GW Colleoni: Cancer / Testis Antigen MAGE-C1 / CT7: new target for multiple myeloma therapy. In: Clinical & developmental immunology. Volume 2012, 2012, p. 257695, doi: 10.1155 / 2012/257695 , PMID 22481966 , PMC 3310219 (free full text).
  3. ↑ a b c d M. F. Gjerstorff, MH Andersen, HJ Ditzel: Oncogenic cancer / testis antigens: prime candidates for immunotherapy. In: Oncotarget. Volume 6, number 18, June 2015, pp. 15772–15787, doi: 10.18632 / oncotarget.4694 , PMID 26158218 , PMC 4599236 (free full text).
  4. ↑ a b A. W. Whitehurst: Cause and consequence of cancer / testis antigen activation in cancer. In: Annual review of pharmacology and toxicology. Volume 54, 2014, pp. 251-272, doi: 10.1146 / annurev-pharmtox-011112-140326 , PMID 24160706 .
  5. ↑ P. Yang, Z. Huo, H. Liao, Q. Zhou: Cancer / testis antigens trigger epithelial-mesenchymal transition and genesis of cancer stem-like cells. In: Current pharmaceutical design. Volume 21, Number 10, 2015, pp. 1292-1300, PMID 25506890 .
  6. ↑ a b M. J. Scanlan, AO Gure, AA Jungbluth, LJ Old, YT Chen: Cancer / testis antigens: an expanding family of targets for cancer immunotherapy. In: Immunological reviews. Volume 188, October 2002, pp. 22-32, PMID 12445278 .
  7. ↑ a b P. Kulkarni, T. Shiraishi, K. Rajagopalan, R. Kim, SM Mooney, RH Getzenberg: Cancer / testis antigens and urological malignancies. In: Nature reviews. Urology. Volume 9, number 7, July 2012, pp. 386-396, doi: 10.1038 / nrurol.2012.117 , PMID 22710665 , PMC 3477645 (free full text).
  8. ↑ O. Hofmann, OL Caballero, BJ Stevenson, YT Chen, T. Cohen, R. Chua, CA Maher, S. Panji, U. Schaefer, A. Kruger, M. Lehvaslaiho, P. Carninci, Y. Hayashizaki, CV Jongeneel, AJ Simpson, LJ Old, W. Hide: Genome-wide analysis of cancer / testis gene expression. In: Proceedings of the National Academy of Sciences . Volume 105, number 51, December 2008, pp. 20422-20427, doi: 10.1073 / pnas.0810777105 , PMID 19088187 , PMC 2603434 (free full text).
  9. ^ BJ Stevenson, C. Iseli, S. Panji, M. Zahn-Zabal, W. Hide, LJ Old, AJ Simpson, CV Jongeneel: Rapid evolution of cancer / testis genes on the X chromosome. In: BMC genomics. Volume 8, 2007, p. 129, doi: 10.1186 / 1471-2164-8-129 , PMID 17521433 , PMC 1890293 (free full text).
  10. ↑ CTdatabase . Retrieved August 4, 2016.
  11. ↑ LG Almeida, NJ Sakabe, AR deOliveira, MC Silva, AS Mundstein, T. Cohen, YT Chen, R. Chua, S. Gurung, S. Gnjatic, AA Jungbluth, OL Caballero, A. Bairoch, E. Kiesler, SL White, AJ Simpson, LJ Old, AA Camargo, AT Vasconcelos: CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens. In: Nucleic acids research. Volume 37, Database issue January 2009, pp. D816-D819, doi: 10.1093 / nar / gkn673 , PMID 18838390 , PMC 2686577 (free full text).
  12. ↑ ACTAbase  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. . Retrieved August 4, 2016.@1@ 2Template: dead link / actabase.jhu.edu