¹Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece

Correspondence: Dr CN Baxevanis, Saint Savas Cancer Hospital, Cancer Immunology and Immunotherapy Center, 171 Alexandras Ave., 11522 Athens, Greece. E-mail: baxevanis@ciic.gr

Revised 3 August 2004; Accepted 13 October 2004; Published online 7 December 2004.

Abstract

Unfractionated peptides (MW: up to 10 kDa), derived from HLA-A2.1 positive (+) HER-2/neu-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-2/neu⁺ autologous primary tumour cells as well as HER-2/neu⁺ tumour cell lines. In addition, adoptive transfer of such CTL significantly prolonged the survival of SCID mice xenografted with HLA-A2.1⁺, HER-2/neu⁺ human breast and ovarian tumour cell lines. Acid cell extracts collected from HLA-A2.1⁺ HER-2/neu negative (-) primary ovarian tumours induced HLA-A2.1-restricted CTL with weak in vitro and in vivo antitumour capacity, suggesting that HER-2/neu peptides within ACE from HER-2/neu-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-2/neu-overexpressing ovarian tumours utilising autologous tumour-derived ACE.