Cytotoxic T Cells Isolated from Ovarian Malignant Ascites Recognize a Peptide Derived from the HER-2/neu Proto-oncogene

The HER-2/neu proto-oncogene encodes a transmembrane receptor protein whose expression is enhanced in a number of breast and ovarian tumors and correlates with tumor aggressiveness, suggesting that it may play an important role in tumor growth. Recent evidence suggests that HER-2/neu may be a potential candidate for targeted immune intervention. In this report we show that cytotoxic T lymphocytes (CTL) expanded from tumor-associated lymphocytes with HLA-A2+ and HER-2/neu+ tumors can specifically recognize synthetic peptides corresponding to amino acids 971-980 of HER-2/neu protein. This sequence includes a potential amphiphilic area containing both Rothbardʹs epitode motifs and HLA-A2 anchor residues. Our study provides the first direct evidence of HER-2/neu-reactive CTL in humans. The fact that these HER-2/neu peptide-reactive CTL show significantly lower reactivity with corresponding EGF-R peptides offers new perspectives for understanding the recognition of self-antigens by tumor-reactive T cells.