Details

Autor(en) / Beteiligte

• Bellone, S
• Tassi, R
• Betti, M
• English, D
• Cocco, E
• Gasparrini, S
• Bortolomai, I
• Black, J D
• Todeschini, P
• Romani, C
• Ravaggi, A
• Bignotti, E
• Bandiera, E
• Zanotti, L
• Pecorelli, S
• Ardighieri, L
• Falchetti, M
• Donzelli, C
• Siegel, E R
• Azodi, M
• Silasi, D-A
• Ratner, E
• Schwartz, P E
• Rutherford, T J
• Santin, A D

Titel

Mammaglobin B (SCGB2A1) is a novel tumour antigen highly differentially expressed in all major histological types of ovarian cancer: implications for ovarian cancer immunotherapy

Ist Teil von

• British journal of cancer, 2013-07, Vol.109 (2), p.462-471

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• Background: We studied the genetic fingerprints of ovarian cancer and validated the potential of Mammaglobin b ( SCGB2A1 ), one of the top differentially expressed genes found in our analysis, as a novel ovarian tumour rejection antigen. Methods: We profiled 70 ovarian carcinomas including 24 serous (OSPC), 15 clear-cell (CC), 24 endometrioid (EAC) and 7 poorly differentiated tumours, and 14 normal human ovarian surface epithelial (HOSE) control cell lines using the Human HG-U133 Plus 2.0 chip (Affymetrix). Quantitative real-time PCR and immunohistochemistry staining techniques were used to validate microarray data at RNA and protein levels for SCGB2A1. Full-length human-recombinant SCGB2A1 was used to pulse monocyte-derived dendritic cells (DCs) to stimulate autologous SCGB2A1-specific cytotoxic T-lymphocyte (CTL) responses against chemo-naive and chemo-resistant autologous ovarian tumours. Results: Gene expression profiling identified SCGB2A1 as a top differentially expressed gene in all histological ovarian cancer types tested. The CD8+ CTL populations generated against SCGB2A1 were able to consistently induce lysis of autologous primary (chemo-naive) and metastatic/recurrent (chemo-resistant) target tumour cells expressing SCGB2A1, whereas autologous HLA-identical noncancerous cells were not lysed. Cytotoxicity against autologous tumour cells was significantly inhibited by anti-HLA-class I (W6/32) monoclonal antibody. Intracellular cytokine expression measured by flow cytometry showed a striking type 1 cytokine profile (i.e., high IFN- γ secretion) in SCGB2A1-specific CTLs. Conclusion: SCGB2A1 is a top differentially expressed gene in all major histological types of ovarian cancers and may represent a novel and attractive target for the immunotherapy of patients harbouring recurrent disease resistant to chemotherapy.