MAGEA3 explained

Melanoma-associated antigen 3 (MAGE-A3) is a protein that in humans is encoded by the MAGEA3 gene.^{[1] [2]}

Genetics

This gene is a member of the melanoma-associated antigen gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita.^[3]

Function and Clinical relevance

The normal function of MAGE-A3 in healthy cells is unknown.^[4] The presence of the antigen on tumor cells has been associated with worse prognosis. In one study, high levels of MAGE-A3 in lung adenocarcinoma were associated with shorter survival.^[5]

MAGE-A3 is a tumor-specific protein, and has been identified on many tumors including melanoma, non-small cell lung cancer, hematologic malignancies, among others.^[6] Currently, GlaxoSmithKline is developing a cancer vaccine targeting MAGE-A3. The vaccine is a fusion protein of MAGE-A3 and Haemophilus influenzae protein D, combined with a proprietary immunoadjuvant.^[7]

Further reading

• Brasseur F, Rimoldi D, Liénard D, etal . Expression of MAGE genes in primary and metastatic cutaneous melanoma . Int. J. Cancer . 63 . 3 . 375–80 . 1995 . 7591235 . 10.1002/ijc.2910630313 . 38676798 .
• Kocher T, Schultz-Thater E, Gudat F, etal . Identification and intracellular location of MAGE-3 gene product . Cancer Res. . 55 . 11 . 2236–9 . 1995 . 7757970 .
• De Plaen E, Arden K, Traversari C, etal . Structure, chromosomal localization, and expression of 12 genes of the MAGE family . Immunogenetics . 40 . 5 . 360–9 . 1994 . 7927540 . 10.1007/BF01246677 . 11331427 .
• Ding M, Beck RJ, Keller CJ, Fenton RG . Cloning and analysis of MAGE-1-related genes . Biochem. Biophys. Res. Commun. . 202 . 1 . 549–55 . 1994 . 8037761 . 10.1006/bbrc.1994.1963 .
• Gaugler B, Van den Eynde B, van der Bruggen P, etal . Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes . J. Exp. Med. . 179 . 3 . 921–30 . 1994 . 8113684 . 10.1084/jem.179.3.921 . 2191409 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Valmori D, Liénard D, Waanders G, etal . Analysis of MAGE-3-specific cytolytic T lymphocytes in human leukocyte antigen-A2 melanoma patients . Cancer Res. . 57 . 4 . 735–41 . 1997 . 9044853 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Mallon AM, Platzer M, Bate R, etal . Comparative Genome Sequence Analysis of the Bpa/Str Region in Mouse and Man . Genome Res. . 10 . 6 . 758–75 . 2000 . 10854409 . 10.1101/gr.10.6.758 . 310879 .
• Jang SJ, Soria JC, Wang L, etal . Activation of melanoma antigen tumor antigens occurs early in lung carcinogenesis . Cancer Res. . 61 . 21 . 7959–63 . 2001 . 11691819 .
• Consogno G, Manici S, Facchinetti V, etal . Identification of immunodominant regions among promiscuous HLA-DR-restricted CD4+ T-cell epitopes on the tumor antigen MAGE-3 . Blood . 101 . 3 . 1038–44 . 2003 . 12393675 . 10.1182/blood-2002-03-0933 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Guo J, Wen DR, Huang RR, etal . Detection of multiple melanoma-associated markers in melanoma cell lines by RT in situ PCR . Exp. Mol. Pathol. . 74 . 2 . 140–7 . 2003 . 12710945 . 10.1016/S0014-4800(03)00012-1 .
• Zerbini A, Pilli M, Soliani P, etal . Ex vivo characterization of tumor-derived melanoma antigen encoding gene-specific CD8+cells in patients with hepatocellular carcinoma . J. Hepatol. . 40 . 1 . 102–9 . 2004 . 14672620 . 10.1016/S0168-8278(03)00484-7 .
• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Zhou M, Peng JR, Zhang HG, etal . Identification of two naturally presented MAGE antigenic peptides from a patient with hepatocellular carcinoma by mass spectrometry . Immunol. Lett. . 99 . 1 . 113–21 . 2005 . 15885805 . 10.1016/j.imlet.2005.02.007 .
• Hudolin T, Juretic A, Spagnoli GC, etal . Immunohistochemical expression of tumor antigens MAGE-A1, MAGE-A3/4, and NY-ESO-1 in cancerous and benign prostatic tissue . Prostate . 66 . 1 . 13–8 . 2006 . 16114059 . 10.1002/pros.20312 . 24732367 .
• Miyagawa N, Kono K, Mimura K, etal . A newly identified MAGE-3-derived, HLA-A24-restricted peptide is naturally processed and presented as a CTL epitope on MAGE-3-expressing gastrointestinal cancer cells . Oncology . 70 . 1 . 54–62 . 2006 . 16446550 . 10.1159/000091185 . 36970406 .

Notes and References

1. van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T . A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma . Science . 254 . 5038 . 1643–7 . Jan 1992 . 1840703 . 10.1126/science.1840703 .
2. Rogner UC, Wilke K, Steck E, Korn B, Poustka A . The melanoma antigen gene (MAGE) family is clustered in the chromosomal band Xq28 . Genomics . 29 . 3 . 725–31 . Mar 1996 . 8575766 . 10.1006/geno.1995.9945 .
3. Web site: Entrez Gene: MAGEA3 melanoma antigen family A, 3.
4. Decoster L, Wauters I, Vansteenkiste JF . Vaccination therapy for non-small-cell lung cancer: review of agents in phase III development . Annals of Oncology . 23 . 6. 1387–1393 . Dec 2011 . 22156658 . 10.1093/annonc/mdr564 . free .
5. Ali O. Gure . Ramon Chua . Barbara Williamson . Mithat Gonen . Cathy A. Ferrera . Sacha Gnjatic . Gerd Ritter . Andrew J.G. Simpson . Yao-T. Chen . Lloyd J. Old . Nasser K. Altorki . Cancer-Testis Genes Are Coordinately Expressed and Are Markers of Poor Outcome in Non–Small Cell Lung Cancer . Clinical Cancer Research . 11 . 22 . 8055–8062 . Nov 2005 . 16299236 . 10.1158/1078-0432.CCR-05-1203 . free .
6. Web site: Corporate Comms . New data on MAGE-A3 cancer immunotherapy support potential novel options of treating non-small cell lung cancer and melanoma . Us.gsk.com . 2012-10-16 . dead . https://web.archive.org/web/20120627085442/http://us.gsk.com/html/media-news/pressreleases/2008/2008_us_pressrelease_10076.htm . 2012-06-27 .
7. Web site: Patent US20100008980 - Use of MAGE A3-Protein D Fusion Antigen in Immunotherapy Combined with ... - Google Patents . 2008-01-08 . 2012-10-16.