De Duve Institute

1. Previous work in our group: Identification of tumor antigens recognized by T cells


In the 1970s it became clear that T lymphocytes, a subset of the white blood cells, were the major effectors of tumor rejection in mice. In the 1980s, human anti-tumor cytolytic T lymphocytes (CTL) were isolated in vitro from the blood lymphocytes of cancer patients, mainly those who had melanoma. Most of these CTL were specific, i.e. they did not kill non-tumor cells. This suggested that they target a marker, or antigen, which is expressed exclusively on tumor cells. We started to study the anti-tumor CTL response of a metastatic melanoma patient and contributed to the definition of several distinct tumor antigens recognized by autologous CTL. In the early 1990s, we identified the gene coding for one of these antigens, and defined the antigenic peptide. This was the first description of a gene, MAGE-A1, coding for a human tumor antigen recognized by T lymphocytes.

Genes such as those of the MAGE family are expressed in many tumors and in male germline cells, but are silent in normal tissues. They are therefore referred to as “cancer-germline genes”. They encode tumor specific antigens, which have been used in therapeutic vaccination trials of cancer patients. A large set of additional cancer-germline genes have now been identified by different approaches, including purely genetic approaches. As a result, a vast number of sequences are known that can code for tumor-specific shared antigens. The identification of a larger set of antigenic peptides, which are presented by HLA class I and class II molecules and recognized on tumors by T lymphocytes, could be important for therapeutic vaccination trials of cancer patients and serve as tools for a reliable monitoring of the immune response of vaccinated patients. To that purpose, we have used various approaches that we have loosely named “reverse immunology”, because they use gene sequences as starting point.

Human tumor antigens recognized by CD4+ or CD8+ T cells are being defined at a regular pace worldwide. Together with colleagues at the de Duve Institute, we read the new publications and incorporate the newly defined antigens in a database accessible at http://www.cancerimmunity.org/peptidedatabase/Tcellepitopes.htm

 


Further reading

van der Bruggen P, Zhang Y, Chaux P, Stroobant V, Panichelli C, Schultz ES, Chapiro J, Van den Eynde BJ, Brasseur F, Boon T.
Tumor-specific shared antigenic peptides recognized by human T cells.
Immunological Reviews. 2002 Oct;188:51-64

van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T.
A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma.
Science. 1991 Dec 13,254(5038): 1643-1647



To know more... (pdf chapter of the last de Duve Institute report)


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