Skip to main content

Advertisement

SpringerLink
Log in

MAGE-C1/CT7 and MAGE-C2/CT10 are frequently expressed in multiple myeloma and can be explored in combined immunotherapy for this malignancy

  • Short communication
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

The exact function of MAGE-C1/CT7 and MAGE-C2/CT10 is not yet understood in multiple myeloma (MM). However, the homologs MAGE-C1/CT7 and MAGE-C2/CT10 genes encode highly immunogeneic cancer/testis antigens (CTAs) and can be potential targets for T cell-based immunotherapy. MAGE-C1/CT7 and MAGE-C2/CT10 mRNA expression were investigated in MM patients, solitary plasmacytomas, monoclonal gammopathies of undetermined significance (MGUS) and bone marrow (BM) aspirates from healthy donors by RT-PCR. MAGE-C1/CT7 and MAGE-C1/CT10 were expressed in 67 and 59 % of the 46 MM analyzed patients. At least one of the genes was expressed in 76 % of MM cases. Solitary plasmacytoma also showed MAGE-C1/CT7 and MAGE-C2/CT10 expression. MAGE-C1/CT7 and MAGE-C2/CT10 were not expressed in normal BM samples, showing restricted expression of these CTA genes in MM, solitary plasmacytoma and MGUS. In the present study, we found high expression of the homologs MAGE-C1/CT7 and MAGE-C2/CT10 in monoclonal gammopathies and speculate whether these genes might represent a valuable therapeutic option for myeloma, in particular for combined immunotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Pingali SR, Haddad RY, Saad A (2012) Current concepts of clinical management of multiple myeloma. Dis Mon 58(4):195–207

    Article  PubMed  Google Scholar 

  2. Rajkumar SV (2012) Multiple myeloma: 2012 update on diagnosis, risk-stratification, and management. Am J Hematol 87(1):78–88

    Article  PubMed  Google Scholar 

  3. Philips S, Menias C, Vikram R et al (2012) Abdominal manifestations of extraosseous myeloma: cross-sectional imaging spectrum. J Comput Assist Tomogr 36(2):207–212

    Article  PubMed  Google Scholar 

  4. Anderson KC (2011) New insights into therapeutic targets in myeloma. Hematol Am Soc Hematol Educ Program 2011:184–190

    Article  Google Scholar 

  5. Morgan GJ, Walker BA, Davies FE (2012) The genetic architecture of multiple myeloma. Nat Rev Cancer 12(5):335–348

    Article  PubMed  CAS  Google Scholar 

  6. de Carvalho F, Vettore AL, Colleoni GW (2012) Cancer/testis antigen MAGE-C1/CT7: new target for multiple myeloma therapy. Clin Dev Immunol 2012:257695

    PubMed  Google Scholar 

  7. Jungbluth AA, Ely S, DiLiberto M et al (2005) The cancer-testis antigens CT7 (MAGE-C1) and MAGE-A3/6 are commonly expressed in multiple myeloma and correlate with plasma-cell proliferation. Blood 106(1):167–174

    Article  PubMed  CAS  Google Scholar 

  8. Simpson AJ, Caballero OL, Jungbluth A et al (2005) Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 5(8):615–625

    Article  PubMed  CAS  Google Scholar 

  9. van der Bruggen P, Traversari C, Chomez P et al (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. J Immunol 178(5):2617–2621

    Google Scholar 

  10. Lucas S, De Smet C, Arden KC et al (1998) Identification of a new MAGE gene with tumor-specific expression by representational difference analysis. Cancer Res 58(4):743–752

    PubMed  CAS  Google Scholar 

  11. Andrade VC, Vettore AL, Felix RS et al (2008) Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients. Cancer Immun 8:2

    PubMed  Google Scholar 

  12. Chen YT, Güre AO, Tsang S et al (1998) Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library. Proc Natl Acad Sci USA 95(2):6919–6923

    Article  PubMed  CAS  Google Scholar 

  13. Güre AO, Stockert E, Arden KC et al (2000) CT10: a new cancer cancer-testis (CT) antigen homologous to CT7 and the MAGE family, identified by representational-difference analysis. Int J Cancer 85(5):726–732

    Article  PubMed  Google Scholar 

  14. Lucas S, De Plaen E, Boon T (2000) MAGE-B5, MAGE-B6, MAGE-C2, and MAGE-C3: four new members of the MAGE Family with tumor-specific expression. Int J Cancer 87(1):55–60

    Article  PubMed  CAS  Google Scholar 

  15. Ma W, Vigneron N, Chapiro J et al (2011) A MAGE-C2 antigenic peptide processed by the immunoproteasome is recognized by cytolytic T cells isolated from a melanoma patient after successful immunotherapy. Int J Cancer 129(10):2427–2434

    Article  PubMed  CAS  Google Scholar 

  16. Curioni-Fontecedro A, Nuber N, Mihic-Probst D et al (2011) Expression of MAGE-C1/CT7 and MAGE-C2/CT10 predicts lymph node metastasis in melanoma patients. PLoS ONE 6(6):e21418

    Article  PubMed  CAS  Google Scholar 

  17. Atanackovic A, Luetkens T, Hildebrandt Y et al (2009) Longitudinal analysis and prognostic effect of cancer-testis antigen expression in multiple myeloma. Clin Cancer Res 15(4):1343–1352

    Article  PubMed  CAS  Google Scholar 

  18. Hofmann O, Caballero OL, Stevenson BJ et al (2008) Genome-wide analysis of cancer/testis gene expression. Proc Natl Acad Sci USA 105(51):20422–20427

    Article  PubMed  CAS  Google Scholar 

  19. Oba-Shinjo SM, Caballero OL, Jungbluth AA et al (2008) Cancer-testis (CT) antigen expression in medulloblastoma. Cancer Immun 8:7

    PubMed  Google Scholar 

  20. de Carvalho F, Costa ET, Camargo AA et al (2011) Targeting MAGE-C1/CT7 expression increases cell sensitivity to the proteasome inhibitor bortezomib in multiple myeloma cell lines. PLoS ONE 6(11):e27707

    Article  PubMed  Google Scholar 

  21. Atanackovic D, Hildebrandt Y, Jadczak A et al (2010) Cancer-testis antigens MAGE-C1/CT7 and MAGE-A3 promote the survival of multiple myeloma cells. Haematologica 95(5):785–793

    Article  PubMed  CAS  Google Scholar 

  22. Anderson LD Jr, Cook DR, Yamamoto TN et al (2011) Identification of MAGE-C1 (CT-7) epitopes for T-cell therapy of multiple myeloma. Cancer Immunol Immunother 60(7):985–997

    Article  PubMed  CAS  Google Scholar 

  23. Ma W, Germeau C, Vigneron N et al (2004) Two new tumor-specific antigenic peptides encoded by gene MAGE-C2 and presented to cytolytic T lymphocytes by HLA-A2. Int J Cancer 109(5):698–702

    Article  PubMed  CAS  Google Scholar 

  24. Caballero OL, Chen YT (2009) Cancer/testis (CT) antigens: potential targets for immunotherapy. Cancer Sci 100(11):2014–2021

    Article  PubMed  CAS  Google Scholar 

  25. Pabst C, Zustin J, Jacobsen F et al (2010) Expression and prognostic relevance of MAGE-C1/CT7 and MAGE-C2/CT10 in osteolytic lesions of patients with multiple myeloma. Exp Mol Pathol 89(2):175–181

    Article  PubMed  CAS  Google Scholar 

  26. Van Nuffel AM, Benteyn D, Wilgenhof S et al (2011) Intravenous and intradermal TriMix-dendritic cell therapy results in a broad T-cell response and durable tumor response in a chemorefractory stage IV-M1c melanoma patient. Cancer Immunol Immunother 61(7):1033–1043

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to Dr. Adriana Seber (Instituto de Oncologia Pediatrica—GRAACC, UNIFESP, São Paulo, Brazil) for normal bone marrow aspirates collected from healthy donors.

Conflict of interest

The authors have declared no conflict of interest.

Author information

Authors and Affiliations

  1. Disciplina de Hematologia e Hemoterapia, Universidade Federal de São Paulo (UNIFESP/EPM), Rua Botucatu, 740, 3o andar, Hematologia, Vila Clementino, CEP 04023-900, São Paulo, Brazil

    Fabricio de Carvalho, Veruska L. F. Alves, Walter M. T. Braga, Celso V. Xavier Jr. & Gisele W. B. Colleoni

Authors
  1. Fabricio de Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Veruska L. F. Alves
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Walter M. T. Braga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Celso V. Xavier Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gisele W. B. Colleoni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabricio de Carvalho.

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Carvalho, F., Alves, V.L.F., Braga, W.M.T. et al. MAGE-C1/CT7 and MAGE-C2/CT10 are frequently expressed in multiple myeloma and can be explored in combined immunotherapy for this malignancy. Cancer Immunol Immunother 62, 191–195 (2013). https://doi.org/10.1007/s00262-012-1376-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-012-1376-4

Keywords

Search

Navigation