In vitro and in vivo induction of a Th cell response toward peptides of the melanoma-associated glycoprotein 100 protein selected by the TEPITOPE program

The melanoma-associated Ag glycoprotein 100 was analyzed by the T cell epit ope prediction software TEPITOPE, Seven HLA-DR promiscuous peptides predict ed with a stringent threshold were used to load dendritic cells (DC), and i nduction of a proliferative response was monitored. PBMC of all nine donors including two patients with malignant melanoma responded to at least one o f the peptides. The proliferative response was defined as a Th response by the selective expansion of CD4(+) cells, up-regulation of CD25 and CD40L, a nd IL-2 and IFN-gamma expression. Peptide-loaded DC also initiated a T help er response in vivo (i.e., tumor growth in the SCID mouse was significantly retarded by the transfer of PBMC together with peptide-loaded DC). Because the use of the TEPITOPE program allows for a prediction of T cell epitopes ; because the predicted peptides can be rapidly confirmed by inducing a Th response in the individual patient; and because application of peptide-load ed DC suffices for the in vive activation of helper cells, vaccination with MHC class II-binding peptides of tumor-associated Ags becomes a feasible a nd likely powerful tool in the immunotherapy of cancer.