A novel human HER2-derived peptide homologous to the mouse K-d-restricted tumor rejection antigen can induce HLA-A24-restricted cytotoxic T lymphocytes in ovarian cancer patients and healthy individuals

A mouse HER2-derived peptide, HER2p63 (A) (TYLPANASL), can induce K-d-restr icted mouse cytotoxic T lymphocytes (CTL) and also function as a tumor reje ction antigen in an in vivo assay. Since the anchor motif of mouse Kd for p eptide binding has much similarity to that of human HLA-A2402, we asked if human HER2p63 (T) (TYLPTNASL) could induce HER2-specific CTL in HLA-A2402-p ositive individuals. Peripheral blood mononuclear cells (PBMC) of HLA-A2402 -positive individuals were sensitized in vitro with HER2p63-pulsed autologo us dendritic cells prepared from PBMC. CTL clone derived from these specifi cally lysed HER2-expressing cell lines bearing HLA-A2402. Cytotoxic activit y of the CTL clone against the HER2-expressing cell line bearing HLA-A2402 was blocked by antibodies against CD3, CD8, HLA-A24 or MHC class I, and was also inhibited by the addition of excess HER2p63-pulsed C1R bearing HLA-A2 402. Killer cells were generated from PBMC of seven healthy individuals and five ovarian cancer patients, all of HLA-A2402 type, by in vitro sensitiza tion with HER2p63-pulsed autologous antigen presenting cells. These killer cells selectively lysed HER2-expressing SKOV3 transfected with HLA-A2402 cD NA, indicating high immunogenicity of HER2p63 in all 12 individuals examine d.