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

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...

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Detalles Bibliográficos
Autores principales: Gritzapis, A D, Perez, S A, Baxevanis, C N, Papamichail, M
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361747/
https://www.ncbi.nlm.nih.gov/pubmed/15583693
http://dx.doi.org/10.1038/sj.bjc.6602259
Descripción
Sumario: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.