Identification of HER-2/neu immunogenic epitopes presented by renal cell carcinoma and other human epithelial tumors

HER-2/neu is a tumor-associated antigen overexpressed in a large variety of human tumors. Eight HER-2/neu peptides displaying HLA-A*0201 anchoring mot ifs were selected and tested for their binding affinity to HLA-A*0201 and t heir capacity to elicit cytotoxic T lymphocyte (CTL) responses in both HLA- A*0201 transgenic mice and in HLA-A*0201(+) healthy donors. Two high-affini ty (p5 and p48) and one intermediate-affinity (p1023) peptides triggered CT L responses in both transgenic mice and humans, comparable to those observe d for the well-known HER2/neu dominant peptide p369. CTL induced in transge nic mice lysed HLA-A*0201(+) RMA cells infected with recombinant HER-2/neu but not cells infected with wild-type vaccinia virus. Human CTL lysed HLA-A *0201 HER-2/neu tumor cells of different origins (breast, colon, lung and r enal cancer) irrespective of the expression levels of HER-2/neu. Importantl y, primed CTL specific for these epitopes were detected in freshly isolated tumor-infiltrating lymphocytes from three renal cell carcinoma patients. T herefore, the HER2/neu peptides p5, p48 and p1023 may be good candidates fo r immunotherapy of a broad spectrum of tumors, including renal cell carcino ma.