MAGE, BAGE and GAGE: tumour antigen expression in benign and malignant ovarian tissue

Abstract

Summary To determine if ovarian cancer patients would be suitable for MAGE-peptide vaccine-based immunotherapy, the frequency of expression of the MAGE-1-4 genes in ovarian tumours was assessed using reverse transcription polymerase chain reaction (RT-PCR) and product verification with digoxigenin-labelled oligonucleotide probes specific for each MAGEgene. In addition, the frequency of expression of more recently discovered tumour antigens (BAGE, GAGE -1, -2 and GAGE -3, -6) was established using RT-PCR and ethidium bromide staining. In this study 1/16 normal ovarian tissue specimens and 11/25 benign lesions expressed MAGE-1. In non-malignant tissue there was preferential expression of MAGE-1 in premenopausal women. A total of 15/27 malignant specimens expressed MAGE-1, including 10/14 serous cystadenocarcinomas. Expression of other tumour antigens was infrequent. The finding of MAGE-1 expression in both benign and malignant tissue questions previous assumptions regarding the role of MAGE genes in carcinogenesis. In addition, preferential MAGE-1 gene expression in non-malignant premenopausal tissue suggests that the MAGE genes may be involved in cellular proliferation as opposed to carcinogenesis or possibly that MAGE gene expression is under cyclical hormonal control. Finally, this study indicates that serous cystadenocarcinomas may be suitable tumours for MAGE-1 peptide immunotherapy.

Identification of HLA-DQα and -DRβ Residues Associated With Susceptibility and Protection to Epithelial Ovarian Cancer

“…Peptides derived from these antigens are recognized by T cells in association with human leukocyte antigen (HLA) class I or class II. In EOC, the expression of tumor antigens such as MAGE, GAGE, and BAGE [24,25], suppressor genes such as p53 [26], protooncogenes such as Hert-2/neu [27], and others [28] has been documented. However, lineage-specific tumor antigens, such as MART-1 and gp100 in melanoma, which are expressed in all tumor cells, have not yet been identified in EOC.…”

A Multipeptide Vaccine is Safe and Elicits T-cell Responses in Participants With Advanced Stage Ovarian Cancer

“…First, ovarian tumors express peptide/major histocompatibility complexes (MHCs), allowing for their recognition by CD8 + T lymphocytes, which are critical for the elimination of tumor cells in vivo. [2][3][4] Second, ovarian tumors express elevated levels of nonmutated proteins such as folate binding protein (FBP), 5,6 Her-2/neu, 7 or melanoma-associated antigen-A1 (MAGE-A1), 8 which could serve as targets for cellular and humoral immune responses. Antigenic peptides from these proteins have been identified, which can be evaluated for immunogenicity in novel vaccine designs.…”

“…The epitopes were chosen on the basis of their MHC restriction and the frequency of expression of the parent protein in ovarian cancers. [6][7][8][12][13][14] In addition, 3 of the peptides (MAGE-A1 161 À 169 , Her-2/neu 369 À 377 , and MAGE-A1 96 À 104 ) were chosen on the basis of their prior immunogenicity in vivo after vaccination. [15][16][17][18] The remaining 2 peptides, FBP 191 À 199 and Her-2/neu 754 À 762 , had not previously been evaluated in humans; however, preclinical data supported incorporation of the peptides into the vaccine.…”

Intraepithelial CD8+tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer

“…The defining characteristics of CT antigens are high expression levels in adult male germ cells, absence of expression in other normal adult tissues, and aberrant expression in a variable proportion of a wide range of different cancer types. Among CT antigens, NY-ESO-1 (13), MAGE-A1 (14), and MAGE-A4 (15) have been reported to be expressed frequently in EOC. The aims of the present study were to examine the significance of various subtypes of TILs in patients with ovarian cancer and to evaluate the relationship between TILs and CT antigen expression.…”