CTpedia (original) (raw)

Project overview

The Cancer-Testis (CT) Antigens are proteins normally expressed only in the human germ line but that are also present in a significant subset of malignant tumors. The practical importance of these proteins is that due to their restricted expression pattern they are frequently recognized by the immune system of cancer patients. Moreover, this antigenicity has raised the possibility of their being used as vaccines to actively stimulate immune responses in order to combat tumor growth. As a result worldwide research into many aspects of CT antigens is rapidly growing prompting the construction of this database as a resource for investigators involved in this area.

Cancer-Testis antigens were first discovered in 1991 when Thierry Boon and his colleagues successfully cloned the first tumor antigen in a ground breaking study that significantly changed the field of tumor immunology (1). It was not immediately recognized that the antigen in question, MAGE-A1, was normally expressed in the germline but it is revealing that subsequent analysis of the pattern of normal tissue expression of all the cancer antigens initially cloned using cytotoxic T-cell clones and autologous tumor mRNA were found to have testis restricted expression amongst normal adult tissues (2, 3). This initial discovery was soon extended through the identification of antigens recognized by antibodies in the sera of cancer patients. One of the first antigens discovere d by this approach was NY-ESO-1 that appears to be the most immunogenic of the CT antigens and that has become the major focus of experimental therapeutic vaccine development within the Ludwig Institute (4).

There are now more than 100 gene families that are strongly upregulated in cancer and where the normal expression is highly biased to the germline. Not all of these have been shown to be capable of eliciting immune responses but are collectively termed the CT antigens.

While significant progress has been made in the development of experimental vaccines incorporating T-Antigens, culminating in the recently announced Phase III trials of MAGE-A3 as a therapeutic vaccine for melanoma and lung cancer, little progress has been made in understanding the function of the gene products in either normal or malignant cells. This is particularly true of the major subset of the CT-Antigens that are encoded on the X chromosome the so called CT-X antigens. Nevertheless, this subset of genes clearly have a number of intriguing properties including their very rapid recent evolution.

This database is aimed at stimulating and providing a reference for further research on CT antigens. and comprises information about each CT gene, its gene products and the immune response induced in cancer patients by these proteins.

If you would like to make contributions to or comment on the database please contact ctdatabase@lncc.br.

References

  1. van der Bruggen, P., Traversari, C., Chomez, P., Lurquin, C., De Plaen, E., Van den Eynde, B., Knuth, A., and Boon, T. (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science (New York, N.Y 254, 1643-1647PMID 1840703
  2. Chen, Y. T., Stockert, E., Chen, Y., Garin-Chesa, P., Rettig, W. J., van der Bruggen, P., Boon, T., and Old, L. J. (1994) Identification of the MAGE-1 gene product by monoclonal and polyclonal antibodies. Proceedings of the National Academy of Sciences of the United States of America 91, 1004-1008PMID 8302824
  3. De Smet, C., Lurquin, C., van der Bruggen, P., De Plaen, E., Brasseur, F., and Boon, T. (1994) Sequence and expression pattern of the human MAGE2 gene. Immunogenetics 39, 121-129PMID 8276455
  4. Chen, Y. T., Scanlan, M. J., Sahin, U., Tureci, O., Gure, A. O., Tsang, S., Williamson, B., Stockert, E., Pfreundschuh, M., and Old, L. J. (1997) A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proceedings of the National Academy of Sciences of the United States of America 94, 1914-1918PMID 9050879