Pooled peptides from HER-2|[sol]|neu-overexpressing primary ovarian tumours induce CTL with potent antitumour responses in vitro and in vivo

摘要

Unfractionated peptides (MW: up to 10?kDa), derived from HLA-A2.1 positive (+) HER-2eu-overexpressing primary tumour cell acid cell extracts (ACE), were successfully used to generate in vitro cytotoxic T lymphocytes (CTL). Primary tumour cells were collected from peritoneal malignant effusions of patients with ovarian cancer. Acid cell extracts-induced CTL specifically lysed in an HLA-A2-restricted manner HER-2eu+ autologous primary tumour cells as well as HER-2eu+ tumour cell lines. In addition, adoptive transfer of such CTL significantly prolonged the survival of SCID mice xenografted with HLA-A2.1+, HER-2eu+ human breast and ovarian tumour cell lines. Acid cell extracts collected from HLA-A2.1+ HER-2eu negative (?) primary ovarian tumours induced HLA-A2.1-restricted CTL with weak in vitro and in vivo antitumour capacity, suggesting that HER-2eu peptides within ACE from HER-2eu-overexpressing primary ovarian tumour cells are immunodominant. The results presented herein serve as a rationale for the initiation of vaccination studies in patients with HER-2eu-overexpressing ovarian tumours utilising autologous tumour-derived ACE.