Natural Antibodies to Tumor-Associated Antigens

  • Sheila María Álvarez-Fernández
  • Lucia De Monte
  • Massimo Alessio
Part of the Methods in Molecular Biology book series (MIMB, volume 1393)


Natural autoantibodies raised by humoral immune response to cancer can be exploited to identify potential tumor-associated antigens (TAAs), and might constitute new putative prognostic and/or diagnostic biomarkers. Here we describe how sera from tumor patients can be used to identify TAAs by screening antibody immunoreactivity against the cancer proteome resolved by two-dimensional gel electrophoresis.

Key words

2D-electrophoresis Immunoproteomics Tumor-associated antigens Autoantibodies Western blot 



M.A. is supported by AIRC. Special Program Molecular Clinical Oncology 5 per mille n.9965, and IG-10538.


  1. 1.
    Tureci O, Sahin U, Pfreundschuh M (1997) Serological analysis of human tumor antigens: molecular definition and implications. Mol Med Today 3:342–349CrossRefPubMedGoogle Scholar
  2. 2.
    Imafuku Y, Omenn GS, Hanash S (2004) Proteomics approaches to identify tumor antigen directed autoantibodies as cancer biomarkers. Dis Markers 20:149–153CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Caron M, Choquet-Kastylevsky G, Joubert-Caron R (2007) Cancer immunomics using autoantibody signatures for biomarker discovery. Mol Cell Proteomics 6:1115–1122CrossRefPubMedGoogle Scholar
  4. 4.
    Mou Z, He Y, Wu Y (2009) Immunoproteomics to identify tumor-associated antigens eliciting humoral response. Cancer Lett 278:123–129CrossRefPubMedGoogle Scholar
  5. 5.
    Zhu Q, Liu M, Dai L et al (2013) Using immunoproteomics to identify tumor-associated antigens (TAAs) as biomarkers in cancer immunodiagnosis. Autoimmun Rev 12:1123–1128, doi: S1568-9972(13)00119-5CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Le Naour F (2001) Contribution of proteomics to tumor immunology. Proteomics 1:1295–1302CrossRefPubMedGoogle Scholar
  7. 7.
    Klade CS, Voss T, Krystek E et al (2001) Identification of tumor antigens in renal cell carcinoma by serological proteome analysis. Proteomics 1:890–898CrossRefPubMedGoogle Scholar
  8. 8.
    De Monte L, Sanvito F, Olivieri S et al (2008) Serological immunoreactivity against colon cancer proteome varies upon disease progression. J Proteome Res 7:504–514CrossRefPubMedGoogle Scholar
  9. 9.
    Tomaino B, Cappello P, Capello M et al (2011) Circulating autoantibodies to phosphorylated alpha-enolase are a hallmark of pancreatic cancer. J Proteome Res 10:105–112CrossRefPubMedGoogle Scholar
  10. 10.
    Zhou W, Capello M, Fredolini C et al (2010) Mass spectrometry analysis of the post-translational modifications of alpha-enolase from pancreatic ductal adenocarcinoma cells. J Proteome Res 9:2929–2936CrossRefPubMedGoogle Scholar
  11. 11.
    Murphy MA, O’Leary JJ, Cahill DJ (2012) Assessment of the humoral immune response to cancer. J Proteomics 75:4573–4579CrossRefPubMedGoogle Scholar
  12. 12.
    Lichtenfels R, Kellner R, Atkins D et al (2003) Identification of metabolic enzymes in renal cell carcinoma utilizing PROTEOMEX analyses. Biochim Biophys Acta 1646:21–31CrossRefPubMedGoogle Scholar
  13. 13.
    Seliger B, Menig M, Lichtenfels R et al (2003) Identification of markers for the selection of patients undergoing renal cell carcinoma-specific immunotherapy. Proteomics 3:979–990CrossRefPubMedGoogle Scholar
  14. 14.
    Unwin RD, Harnden P, Pappin D et al (2003) Serological and proteomic evaluation of antibody responses in the identification of tumor antigens in renal cell carcinoma. Proteomics 3:45–55CrossRefPubMedGoogle Scholar
  15. 15.
    Prasannan L, Misek DE, Hinderer R et al (2000) Identification of beta-tubulin isoforms as tumor antigens in neuroblastoma. Clin Cancer Res 6:3949–3956PubMedGoogle Scholar
  16. 16.
    Cui JW, Li WH, Wang J et al (2005) Proteomics-based identification of human acute leukemia antigens that induce humoral immune response. Mol Cell Proteomics 4:1718–1724CrossRefPubMedGoogle Scholar
  17. 17.
    Forgber M, Gellrich S, Sharav T et al (2009) Proteome-based analysis of serologically defined tumor-associated antigens in cutaneous lymphoma. PLoS One. doi: 10.1371/journal.pone.0008376 Google Scholar
  18. 18.
    Forgber M, Trefzer U, Sterry W et al (2009) Proteome serological determination of tumor-associated antigens in melanoma. PLoS One. doi: 10.1371/journal.pone.0005199 Google Scholar
  19. 19.
    Le Naour F, Brichory F, Misek DE et al (2002) A distinct repertoire of autoantibodies in hepatocellular carcinoma identified by proteomic analysis. Mol Cell Proteomics 1:197–203CrossRefPubMedGoogle Scholar
  20. 20.
    Brichory F, Beer D, Le Naour F et al (2001) Proteomics-based identification of protein gene product 9.5 as a tumor antigen that induces a humoral immune response in lung cancer. Cancer Res 61:7908–7912PubMedGoogle Scholar
  21. 21.
    Cui L, Zhiqiang X, Zhuchu C et al (2006) Proteome analysis of human lung squamous carcinoma. Proteomics 6:547–558CrossRefGoogle Scholar
  22. 22.
    He P, Naka T, Serada S et al (2007) Proteomics-based identification of alpha-enolase as a tumor antigen in non-small lung cancer. Cancer Sci 98:1234–1240CrossRefPubMedGoogle Scholar
  23. 23.
    Le Naour F, Misek DE, Krause MC et al (2001) Proteomics-based identification of RS/DJ-1 as a novel circulating tumor antigen in breast cancer. Clin Cancer Res 7:3328–3335PubMedGoogle Scholar
  24. 24.
    Hamrita B, Chahed K, Kabbage M et al (2008) Identification of tumor antigens that elicit a humoral immune response in breast cancer patients’ sera by serological proteome analysis (SERPA). Clin Chim Acta 393:95–102CrossRefPubMedGoogle Scholar
  25. 25.
    Hong SH, Misek DE, Wang H et al (2004) An autoantibody-mediated immune response to calreticulin isoforms in pancreatic cancer. Cancer Res 64:5504–5510CrossRefPubMedGoogle Scholar
  26. 26.
    Tomaino B, Cappello P, Capello M et al (2007) Autoantibody signature in human ductal pancreatic adenocarcinoma. J Proteome Res 6:4025–4031CrossRefPubMedGoogle Scholar
  27. 27.
    Tsunemi S, Nakanishi T, Fujita Y et al (2010) Proteomics-based identification of a tumor-associated antigen and its corresponding autoantibody in gastric cancer. Oncol Rep 23:949–956PubMedGoogle Scholar
  28. 28.
    He Y, Wu Y, Mou Z et al (2007) Proteomics-based identification of HSP60 as a tumor-associated antigen in colorectal cancer. Proteomics Clin Appl 1:336–342CrossRefPubMedGoogle Scholar
  29. 29.
    He Y, Mou Z, Li W et al (2009) Identification of IMPDH2 as a tumor-associated antigen in colorectal cancer using immunoproteomics analysis. Int J Colorectal Dis 24:1271–1279CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Sheila María Álvarez-Fernández
    • 1
  • Lucia De Monte
    • 2
  • Massimo Alessio
    • 1
  1. 1.Proteome Biochemistry UnitIRCCS San Raffaele HospitalMilanoItaly
  2. 2.Tumor Immunology UnitIRCCS San Raffaele HospitalMilanoItaly

Personalised recommendations