MAGE‐A10 is a nuclear protein frequently expressed in high percentages of tumor cells in lung, skin and urothelial malignancies

Abstract

MAGE‐A10 is a highly immunogenic member of the MAGE‐A family of cancer/testis tumor‐associated antigens (C/T TAAs). Studies performed with broadly reactive antibodies have helped to initially characterize this TAA. However, no specific reagents have been developed so far, thus preventing a thorough analysis of its expression in healthy and tumoral tissues. We have produced MAGE‐A10 gene product in soluble recombinant form, and we have used it to generate specific monoclonal antibodies (mAbs). One of these reagents, recognizing an epitope located at the COOH terminus of the MAGE‐A10 gene product, was used to stain a multitumor tissue microarray comprising more than 2,500 paraffin‐embedded specimens including healthy tissues, benign tumors and malignancies of different histological origin. MAGE‐A10 protein was identified as an intranuclear protein of an apparent molecular weight of 70 kDa, expressed in normal spermatogonia and spermatocytes but in no other healthy tissue. Most importantly, this C/T TAA appears to be expressed in high (>50%) percentages of cancer cells from a number of malignancies, including lung, skin and urothelial tumors. Unexpectedly, high expression of MAGE‐A10 TAA at the protein level was also detectable in gynecological malignancies and stomach and gall bladder cancers. The characterization of MAGE‐A10‐specific reagents might set the stage for the development of targeted active immunotherapy by clarifying potential indications and by allowing the selection of patients eligible for treatment and the monitoring of its effectiveness.

High expression of MAGE-A10 cancer-testis antigen in triple-negative breast cancer

“…Different results observed between studies may be due to different antibodies used for CT detection or difference in scoring system. Some authors define positive CT-X antigen expression according to percentage of cells [21,28,29], while others combine the extent and intensity of CT expression using semi-quantitative scoring systems [30,31]. In addition, TMA-based analyses are likely to have a higher falsenegative rate due to sampling error, since CTA expression in tumors is frequently focal.…”

“…For the detection of MAGE-A10 protein, we used undiluted 3DA3 mAb, whereas [21] undiluted B9.8.1.1 mAb was utilized for NY-ESO-1 detection [22]. TMA staining was described in detail elsewhere [23].…”

MAGEA10 gene expression in non-small cell lung cancer and A549 cells, and the affinity of epitopes with the complex of HLA-A∗0201 alleles

“…In addition, MAGEA10 has been recently found in about 1/3 of several cancers, which also showed strong correlation between MAGE-A10 staining score with tumor grade and stage [46,47], and the massive amplification of MAGEA10 (254-262) epitopes by engineered bacteriophages to induce strong antitumor CTL responses in vivo and in vitro [48], which all show that MAGEA10 remain to be a important target from research to clinic, especially for cancer immunotherapy.…”

T-Cell Receptor Gene Therapy: Critical Parameters for Clinical Success

“…Cancer/testis (C/T) antigens are expressed in various human cancers, and also in the human germ line (van der Bruggen et al, 1991;Jager et al, 1998;Simpson et al, 2005). Expression of C/T antigens in other healthy tissues is generally presumed to be absent (Rimoldi et al, 1999;Caballero and Chen, 2009;Schultz-Thater et al, 2011), which marks them as the class of shared TAAs with the most restricted expression pattern in untransformed cells. There is evidence though that at least certain C/T antigens can be expressed by thymic epithelial cells, suggesting that there may be some level of T-cell tolerance toward these antigens.…”

“…expression in all normal tissues that can be accessed by the immune system seems to be absent (Rimoldi et al, 1999;Caballero and Chen, 2009;Schultz-Thater et al, 2011). Second, for many C/T antigens, expression is observed in various human cancers (Simpson et al, 2005), which means that relatively large groups of patients can potentially be treated.…”