Les antigènes associés aux tumeurs humaines: De leur identification à leur utilisation thérapeutique

It is now well established that malignant transformation of human cells may be associated with the expression of tumor antigens that are recognized by cancer patient T-lymphocytes. Most of these antigens consist of antigenic peptides that are presented to T-cells by human histocompatibility leukocyte antigen (HLA) molecules. Several strategies have been developed to characterize tumor antigens recognized by cytotoxic (CTL) and helper (Th) T- lymphocytes. The genetic approach, based on HLA gene and tumor cell line cDNA library transfection in recipient cells to isolate the gene producing the antigenic peptide and the biochemical approach based on the purification and sequence of the tumor peptide have been successfully used. The identified tumor antigens have been classified in at least four categories: Tumor specific antigens encoded by genes that are exclusively expressed in tumors but lacking in normal tissues except testis, differentiation antigens and antigens encoded by mutated or over-expressed genes. Some of these antigens are sufficiently tumorspecific and provide opportunities for the development of therapeutic strategies against cancer. Vaccination trials with these tumor antigens are now under investigation particulary in melanoma patients.