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TCR T-cell therapies are currently being studied to determine safety and efficacy through clinical trials.

MAGE-A4 is expressed across cancer types such as SyS, MRCLS, melanoma, HNSCC, NSCLC, EGJ, ovarian, esophageal, and gastric cancers

Cancer/testis antigens (CTAs) such as MAGE-A4 are tumor antigen proteins that are promising targets for cancer immunotherapies due to this aberrant expression in many tumor types, with no or low expression in normal adult somatic tissues2,3

Cancer Testis Antigens expression chart
  • CTAs form a family of antigens encoded by 276 genes, comprising more than 70 gene families4
  • CTAs can be reexpressed in a variety of cancers4
  • Many members of the CTA family have been shown to elicit spontaneous cellular and humoral immune responses in cancer patients, suggesting immunogenicity of the proteins4
  • The biological functions of CTAs are still being characterized; however, overexpression in various cancers is associated with high tumor grade and poor prognosis2

Incidence of MAGE-A4 expression by tumor type5-12

MAGE A4 expression table

*By immunohistochemical analysis of tumor tissues from confirmed SyS cases.6

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Review information about MAGE-A4 testing and the role of biomarkers for TCR T-cell therapies.

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EGJ=esophagogastric junction; HNSCC=head and neck squamous cell carcinoma; MAGE-A4=melanoma-associated antigen A4; MRCLS=myxoid/round cell liposarcoma; NSCLC=non-small cell lung cancer; SyS=synovial sarcoma; TCR=T-cell receptor.

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References

  1. Wang T, Navenot JM, Rafail S, et al. Identifying MAGE-A4–positive tumors for SPEAR T-cell therapies in HLA-A*02–eligible patients. Presented at: American Association for Cancer Research Annual Meeting; April 8-13, 2022; New Orleans, LA. Poster LB001.
  2. Poojary M, Jishnu PV, Kabekkodu SP. Prognostic value of melanoma-associated antigen-A (MAGE-A) gene expression in various human cancers: a systematic review and meta-analysis of 7428 patients and 44 studies. Mol Diagn Ther. 2020;24(5):537-555.
  3. Ai H, Yang H, Li L, Ma J, Liu K, Li Z. Cancer/testis antigens: promising immunotherapy targets for digestive tract cancers. Front Immunol. 2023;14:1-14.
  4. Thomas R, Al-Khadairi G, Roelands J, et al. NY-ESO-1 based immunotherapy of cancer: current perspectives. Front Immunol. 2018;9:947.
  5. Mitchell G, Pollack SM, Wagner MJ. Targeting cancer testis antigens in synovial sarcoma. J Immunother Cancer. 2021;9(6):e002072.
  6. Iura K, Maekawa A, Kohashi K, et al. Cancer-testis antigen expression in synovial sarcoma: NYO-ESO-1, PRAME, MAGEA4, and MAGEA1. Hum Pathol. 2017;61:130-139.
  7. Sharma P, Shen Y, Wen S, et al. Cancer-testis antigens: expression and correlation with survival in human urothelial carcinoma. Clin Cancer Res. 2006;12(18):5442-5447.
  8. Ishihara M, Kageyama S, Miyahara Y, et al. MAGE-A4, NY-ESO-1 and SAGE mRNA expression rates and co-expression relationships in solid tumours. BMC Cancer. 2020;20(1):606.
  9. Zhang Y, Zhang Y, Zhang L. Expression of cancer–testis antigens in esophageal cancer and their progress in immunotherapy. J Cancer Res Clin Oncol. 2019;145(2):281-291.
  10. Weon JL, Potts PR. The MAGE protein family and cancer. Curr Opin Cell Biol. 2015;37:1-8.
  11. Barrow C, Browning J, MacGregor D, et al. Tumor antigen expression in melanoma varies according to the antigen and stage. Clin Cancer Res. 2006;12(3 pt 1):764-771.
  12. Laban S, Atanackobvic D, Luetkens T, et al. Simultaneous cytoplasmic and nuclear protein expression of melanoma antigen-A family and NY-ESO-1 cancer-testis antigens represents an independent marker for poor survival in head and neck cancer. Int J Cancer. 2014;135(5):1142-1152.