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


ABSTRACT:

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-? 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.

SUBMITTER: Bellone S 

PROVIDER: S-EPMC3721400 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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

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

British journal of cancer 20130627 2


<h4>Background</h4>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.<h4>Methods</h4>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  ...[more]

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