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Contenuto archiviato il 2024-04-16

CELL SURFACE PROPERTIES AND TUMOUR SPECIFIC ANTIGENS: ROLE OF METATSTASIS AND HOST IMMUNE RESPONSE

Obiettivo

The objective is to improve our knowledge of the tumour cell properties that influence the specific immune response of the host and also the ability of tumour cells to invade surrounding tissues and to metastasise. This should lead to the development of new treatment by increasing the specific host immune response and by inhibiting the invasive potential of tumour cells.
Research has been carried out in order to understand the cell surface properties of human tumour cells that are the target of cellular immune defences of the host and also those cell surface properties that make human cells more or less prone to invade surrounding tissues and metastasize. Progress in the understanding of these functions will be applied to inhibit metastasis and to stimulate the specific T-cell mediated immune defences of cancer patients.

The first gene coding for an antigen recognized by autologous T-lymphocytes on a human melanoma has been identified. This was achieved by transfection of a gene library from the melanoma and detection of the transfectants expressing the antigen by their ability to stimulate the production of tumour necrosis factor by the antitumour cytolytic T-lymphocyte (CTL) clone. This new gene, named MAGE-1 (for melanoma antigen), is not expressed in any normal adult tissue tested, with the exception of testis. Gene MAGE-1 is expressed however, by 40% of melanomas, 30% of lung tumours, 15% of the breast tumours and 25% of head and neck tumours, as indicated by the screening of a bank of human tumours. The tumour rejection antigen encoded by gene MAGE-1 and recognized by the antitumour CTL clone is a nonapeptide derived by the MAGE-1 protein and presented at the cell surface by the HLA-A1 molecule. Hence several human cell lines expressing gene MAGE-1 and derived from HLA-A1+ patients express this MAGE-1 derived tumour antigen and are lysed by the same CTL clone.

These results validate the approach of using autologous CTL to identify genes that code for tumour rejection antigens and open the possibility of vaccinating cancer patients with a defined antigen.
Central to this project is the obtention and storage of freshly collected tumour material and the development of permanent tumour cell lines on which both the cell surface properties relevant for metastasis and the tumour-specific antigens may then be studied in detail by all the participating centers. In a first step, the histology of the collected tumours will be restricted to melanomas, sarcomas, ovarian, breast and colon carcinomas. Tumour specimens, reagents and scientific knowledge will be exchanged. Patients with these types of tumours will be selected by the participating groups and attempts will be made by some of the group to establish permanent cell lines. These cell lines will then be sent back to all groups for specific studies of their invasion-related properties and of their immunogenecity to autologous T lymphocytes.

Campo scientifico (EuroSciVoc)

CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: Il Vocabolario Scientifico Europeo.

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CON - Coordination of research actions

Coordinatore

Ludwig Institute for Cancer Research
Contributo UE
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Indirizzo
Avenue Hippocrate 74
1200 Brussels
Belgio

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