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 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.
Gritzapis
A D
AD
Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece.
Perez
S A
SA
Baxevanis
C N
CN
Papamichail
M
M
D019264:Adoptive Transfer; D000818:Animals; D002457:Cell Extracts; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D002457:Cell Extracts; D016207:Cytokines; D016056:Immunodominant Epitopes; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases