Naturally occurring human lymphocyte antigen-A2 restricted CD8+T-cell response to the cancer testis antigen NY-ESO-1 in melanoma patients

Cancer testis (CT) antigens are particularly interesting candidates for can ter vaccines. However, T-cell reactivity to CT antigens has been detected o nly occasionally In cancer patients, even after vaccination. A new group of CT antigens has been recently identified using the SEREX technique based o n immunoscreening of tumor cDNA expression libraries with autologous sera. We have used fluorescent HLA-A2/peptide tetramers containing an optimized a ntigenic peptide to directly identify HLA-A2-restricted CD8(+) T cells spec ific for the SEREX-defined CT antigen NY-ESO-1 in melanoma patients. High f requencies of NY-ESO-1-specific CD8+ T cells were readily detected in pepti de-stimulated peripheral blood mononuclear cells as well as in lymphocytes infiltrating melanoma lesions from patients with measurable antibody respon ses to NY-ESO-1. NY-ESO-1-specific CD8(+) T cells were also detectable in p eptide-stimulated peripheral blood mononuclear cells from some seronegative patients. Whereas the frequencies of NY-ESO-1-specific CD8(+) T cells in c irculating lymphocytes were usually below the limit of detection by tetrame r staining, the presence of NY-ESO-I CD8+ T cells displaying a memory pheno type was clearly detectable ex vivo in blood from a seropositive patient ov er an extended period of time. These results indicate that sustained CD8(+) T-cell responses to CT antigens can naturally occur both locally and syste mically in melanoma patients.