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-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.

RETRACTED ARTICLE: Targeted immune therapy of ovarian cancer

“…In a recent study by Tassi, mammaglobin B was found to be highly overexpressed in nearly 50% of ovarian cancer specimens and high level expression independently correlated with a better outcome [198-200]. Bellone and colleagues [201] subsequently showed that it was highly immunogenic as can generate robust antibody responses and containing T cell epitopes.…”

Clostridium perfringens enterotoxin C‐terminal domain labeled to fluorescent dyes for in vivo visualization of micrometastatic chemotherapy‐resistant ovarian cancer

“…Claudin-3/4 were recently found by our group as well as others to be preferentially overexpressed in multiple histological types of ovarian cancer 9–12 . Interestingly, these receptors were found to be more expressed in chemotherapy-resistant ovarian cancers when compared to chemotherapy-naïve ovarian tumors as well as in the subpopulation of CD44-positive cancer cells with stem cells properties, thought to be responsible for the development of drug resistance and tumor relapse 13, 14, 2615 .…”

“…Our research group has analyzed the genetic fingerprints of a large number of epithelial ovarian cancers 9–12 . In these studies we discovered Claudin-3 and Claudin-4 as two of the top differentially expressed genes in all histological ovarian cancer types tested 9–12 .…”

Claudins Overexpression in Ovarian Cancer: Potential Targets for Clostridium Perfringens Enterotoxin (CPE) Based Diagnosis and Therapy

“…Ovarian cancers of varying subtypes including mucinous, serous, undifferentiated, clear cell, and endometrioid carcinomas have been found to highly express claudin-3 and claudin-4 but normal ovarian surface epithelium does not [14,59,81–83] (Table 2). This data suggests that the low-level expression of these claudins is associated with a benign condition and that high expression is more likely to be a signal of a malignant transformation.…”