Skip to main content

Advertisement

SpringerLink
Log in

Oncoantigens as anti-tumor vaccination targets: the chance of a lucky strike?

  • Symposium Paper
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Neoplastic transformation is a multistage process and distinct gene products of specific cell regulatory pathways are involved at each stage. Identification of genes overexpressed at a specific stage provides an unprecedented opportunity to address the immune system against antigens with a driving role in tumor progression (oncoantigens). The ERBB2 oncogene is a prototype of deregulated oncogenic protein kinase membrane receptors. Mice transgenic for rat ERBB2 (BALB-neuT mice) were used in this study to identify an additional set of oncoantigens expressed at defined stages by most breast carcinomas to be used as alternatives to ERBB2-driven vaccination. To address this question, we integrated the transcription data generated by comparing preneoplastic lesions and neoplasia in BALB-neuT mice with a meta-analysis on transcription profiles generated from normal and breast tumor human specimens. Forty-six putative oncoantigens identified and prioritized according to their expression on the cell membrane or in the extra cellular space, cytoplasm and nucleus were chosen for preclinical investigation as vaccination targets.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Alinari L, Lapalombella R, Andritsos L, Baiocchi RA, Lin TS, Byrd JC (2007) Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic leukemia. Oncogene 26:3644–3653

    Article  PubMed  CAS  Google Scholar 

  2. Altieri DC (2003) Validating survivin as a cancer therapeutic target. Nat Rev Cancer 3:46–54

    Article  PubMed  CAS  Google Scholar 

  3. Astolfi A, Landuzzi L, Nicoletti G, De Giovanni C, Croci S, Palladini A, Ferrini S, Iezzi M, Musiani P, Cavallo F, Forni G, Nanni P, Lollini PL (2005) Gene expression analysis of immune-mediated arrest of tumorigenesis in a transgenic mouse model of HER-2/neu-positive basal-like mammary carcinoma. Am J Pathol 166:1205–1216

    PubMed  CAS  Google Scholar 

  4. Ben-Baruch A (2006) The multifaceted roles of chemokines in malignancy. Cancer Metastasis Rev 25:357–371

    Article  PubMed  CAS  Google Scholar 

  5. Boggio K, Nicoletti G, Di Carlo E, Cavallo F, Landuzzi L, Melani C, Giovarelli M, Rossi I, Nanni P, De Giovanni C, Bouchard P, Wolf S, Modesti A, Musiani P, Lollini PL, Colombo MP, Forni G (1998) Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of Her-2/neu transgenic mice. J Exp Med 188:589–596

    Article  PubMed  CAS  Google Scholar 

  6. Breitling R, Armengaud P, Amtmann A, Herzyk P (2004) Rank products: a simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments. FEBS Lett 573:83–92

    Article  PubMed  CAS  Google Scholar 

  7. Calogero RA, Cordero F, Forni G, Cavallo F (2007) Inflammation and breast cancer. Inflammatory component of mammary carcinogenesis in ErbB2 transgenic mice. Breast Cancer Res 9:211

    Article  PubMed  CAS  Google Scholar 

  8. Cavallo F, Astolfi A, Iezzi M, Cordero F, Lollini PL, Forni G, Calogero R (2005) An integrated approach of immunogenomics and bioinformatics to identify new tumor associated antigens (TAA) for mammary cancer immunological prevention. BMC Bioinformatics 6(Suppl 4):S7

    Article  PubMed  CAS  Google Scholar 

  9. Cavallo F, Calogero RA, Forni G (2007) Are oncoantigens suitable targets for anti-tumour therapy? Nat Rev Cancer 7:707–713

    Article  PubMed  CAS  Google Scholar 

  10. Cavallo F, Offringa R, van der Burg SH, Forni G, Melief CJ (2006) Vaccination for treatment and prevention of cancer in animal models. Adv Immunol 90:175–213

    Article  PubMed  CAS  Google Scholar 

  11. Chen FH, Thomas AO, Hecht JT, Goldring MB, Lawler J (2005) Cartilage oligomeric matrix protein/thrombospondin 5 supports chondrocyte attachment through interaction with integrins. J Biol Chem 280:32655–32661

    Article  PubMed  CAS  Google Scholar 

  12. Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL, Lapuk A, Neve RM, Qian Z, Ryder T, Chen F, Feiler H, Tokuyasu T, Kingsley C, Dairkee S, Meng Z, Chew K, Pinkel D, Jain A, Ljung BM, Esserman L, Albertson DG, Waldman FM, Gray JW (2006) Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 10:529–541

    Article  PubMed  CAS  Google Scholar 

  13. Cho WC, Yip TT, Yip C, Yip V, Thulasiraman V, Ngan RK, Lau WH, Au JS, Law SC, Cheng WW, Ma VW, Lim CK (2004) Identification of serum amyloid a protein as a potentially useful biomarker to monitor relapse of nasopharyngeal cancer by serum proteomic profiling. Clin Cancer Res 10:43–52

    Article  PubMed  CAS  Google Scholar 

  14. Chong IW, Chang MY, Chang HC, Yu YP, Sheu CC, Tsai JR, Hung JY, Chou SH, Tsai MS, Hwang JJ, Lin SR (2006) Great potential of a panel of multiple hMTH1, SPD, ITGA11 and COL11A1 markers for diagnosis of patients with non-small cell lung cancer. Oncol Rep 16:981–988

    PubMed  CAS  Google Scholar 

  15. Desmedt C, Piette F, Loi S, Wang Y, Lallemand F, Haibe-Kains B, Viale G, Delorenzi M, Zhang Y, d’Assignies MS, Bergh J, Lidereau R, Ellis P, Harris AL, Klijn JG, Foekens JA, Cardoso F, Piccart MJ, Buyse M, Sotiriou C (2007) Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res 13:3207–3214

    Article  PubMed  CAS  Google Scholar 

  16. Dohi T, Beltrami E, Wall NR, Plescia J, Altieri DC (2004) Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis. J Clin Invest 114:1117–1127

    PubMed  CAS  Google Scholar 

  17. Domagala A, Kurpisz M (2001) CD52 antigen—a review. Med Sci Monit 7:325–331

    PubMed  CAS  Google Scholar 

  18. Gagarina V, Carlberg AL, Pereira-Mouries L, Hall DJ (2008) Cartilage oligomeric matrix protein (COMP) protects cells against death by elevating members of the IAP family of survival proteins. J Biol Chem 283(1):648–659

    Article  PubMed  CAS  Google Scholar 

  19. Ghosh D (2003) Penalized discriminant methods for the classification of tumors from gene expression data. Biometrics 59:992–1000

    Article  PubMed  Google Scholar 

  20. Giuliani N, Bonomini S, Romagnani P, Lazzaretti M, Morandi F, Colla S, Tagliaferri S, Lasagni L, Annunziato F, Crugnola M, Rizzoli V (2006) CXCR3 and its binding chemokines in myeloma cells: expression of isoforms and potential relationships with myeloma cell proliferation and survival. Haematologica 91:1489–1497

    PubMed  CAS  Google Scholar 

  21. Guo P, Imanishi Y, Cackowski FC, Jarzynka MJ, Tao HQ, Nishikawa R, Hirose T, Hu B, Cheng SY (2005) Up-regulation of angiopoietin-2, matrix metalloprotease-2, membrane type 1 metalloprotease, and laminin 5 gamma 2 correlates with the invasiveness of human glioma. Am J Pathol 166:877–890

    PubMed  CAS  Google Scholar 

  22. Gutfeld O, Prus D, Ackerman Z, Dishon S, Linke RP, Levin M, Urieli-Shoval S (2006) Expression of serum amyloid A, in normal, dysplastic, and neoplastic human colonic mucosa: implication for a role in colonic tumorigenesis. J Histochem Cytochem 54:63–73

    Article  PubMed  CAS  Google Scholar 

  23. Hata T, Furukawa T, Sunamura M, Egawa S, Motoi F, Ohmura N, Marumoto T, Saya H, Horii A (2005) RNA interference targeting aurora kinase a suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells. Cancer Res 65:2899–2905

    Article  PubMed  CAS  Google Scholar 

  24. Howard BA, Wang MZ, Campa MJ, Corro C, Fitzgerald MC, Patz EF Jr (2003) Identification and validation of a potential lung cancer serum biomarker detected by matrix-assisted laser desorption/ionization-time of flight spectra analysis. Proteomics 3:1720–1724

    Article  PubMed  CAS  Google Scholar 

  25. Ivshina AV, George J, Senko O, Mow B, Putti TC, Smeds J, Lindahl T, Pawitan Y, Hall P, Nordgren H, Wong JE, Liu ET, Bergh J, Kuznetsov VA, Miller LD (2006) Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer. Cancer Res 66:10292–10301

    Article  PubMed  CAS  Google Scholar 

  26. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449:557–563

    Article  PubMed  CAS  Google Scholar 

  27. Kirchhofer D, Peek M, Lipari MT, Billeci K, Fan B, Moran P (2005) Hepsin activates pro-hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor-1B (HAI-1B) and HAI-2. FEBS Lett 579:1945–1950

    Article  PubMed  CAS  Google Scholar 

  28. Kominsky SL (2006) Claudins: emerging targets for cancer therapy. Expert Rev Mol Med 8:1–11

    Article  PubMed  Google Scholar 

  29. Kominsky SL, Tyler B, Sosnowski J, Brady K, Doucet M, Nell D, Smedley JG, 3rd, McClane B, Brem H, Sukumar S (2007) Clostridium perfringens enterotoxin as a novel-targeted therapeutic for brain metastasis. Cancer Res 67:7977–7982

    Article  PubMed  CAS  Google Scholar 

  30. Koyama K, Ito K, Hasegawa A (2007) Role of male reproductive tract CD52 (mrt-CD52) in reproduction. Soc Reprod Fertil Suppl 63:103–110

    PubMed  CAS  Google Scholar 

  31. Krambeck AE, Thompson RH, Dong H, Lohse CM, Park ES, Kuntz SM, Leibovich BC, Blute ML, Cheville JC, Kwon ED (2006) B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival. Proc Natl Acad Sci USA 103:10391–10396

    Article  PubMed  CAS  Google Scholar 

  32. Kryczek I, Zou L, Rodriguez P, Zhu G, Wei S, Mottram P, Brumlik M, Cheng P, Curiel T, Myers L, Lackner A, Alvarez X, Ochoa A, Chen L, Zou W (2006) B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med 203:871–881

    Article  PubMed  CAS  Google Scholar 

  33. Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P (2003) An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med 197:1537–1549

    Article  PubMed  CAS  Google Scholar 

  34. Lindberg P, Larsson A, Nielsen BS (2006) Expression of plasminogen activator inhibitor-1, urokinase receptor and laminin gamma-2 chain is an early coordinated event in incipient oral squamous cell carcinoma. Int J Cancer 118:2948–2956

    Article  PubMed  CAS  Google Scholar 

  35. Liotta LA, Kohn EC (2001) The microenvironment of the tumour-host interface. Nature 411:375–379

    Article  PubMed  CAS  Google Scholar 

  36. Lollini PL, Cavallo F, Nanni P, Forni G (2006) Vaccines for tumour prevention. Nat Rev Cancer 6:204–216

    Article  PubMed  CAS  Google Scholar 

  37. Masuelli L, Focaccetti C, Cereda V, Lista F, Vitolo D, Trono P, Gallo P, Amici A, Monaci P, Mattei M, Modesti M, Forni G, Kraus MH, Muraro R, Modesti A, Bei R (2007) Gene-specific inhibition of breast carcinoma in BALB-neuT mice by active immunization with rat Neu or human ErbB receptors. Int J Oncol 30:381–392

    PubMed  CAS  Google Scholar 

  38. Miller LD, Smeds J, George J, Vega VB, Vergara L, Ploner A, Pawitan Y, Hall P, Klaar S, Liu ET, Bergh J (2005) An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. Proc Natl Acad Sci USA 102:13550–13555

    Article  PubMed  CAS  Google Scholar 

  39. Pawitan Y, Bjohle J, Amler L, Borg AL, Egyhazi S, Hall P, Han X, Holmberg L, Huang F, Klaar S, Liu ET, Miller L, Nordgren H, Ploner A, Sandelin K, Shaw PM, Smeds J, Skoog L, Wedren S, Bergh J (2005) Gene expression profiling spares early breast cancer patients from adjuvant therapy: derived and validated in two population-based cohorts. Breast Cancer Res 7:R953–R964

    Article  PubMed  CAS  Google Scholar 

  40. Quaglino E, Iezzi M, Mastini C, Amici A, Pericle F, Di Carlo E, Pupa SM, De Giovanni C, Spadaro M, Curcio C, Lollini PL, Musiani P, Forni G, Cavallo F (2004) Electroporated DNA vaccine clears away multifocal mammary carcinomas in her-2/neu transgenic mice. Cancer Res 64:2858–2864

    Article  PubMed  CAS  Google Scholar 

  41. Quaglino E, Rolla S, Iezzi M, Spadaro M, Musiani P, De Giovanni C, Lollini PL, Lanzardo S, Forni G, Sanges R, Crispi S, De Luca P, Calogero R, Cavallo F (2004) Concordant morphologic and gene expression data show that a vaccine halts HER-2/neu preneoplastic lesions. J Clin Invest 113:709–717

    PubMed  CAS  Google Scholar 

  42. Salceda S, Tang T, Kmet M, Munteanu A, Ghosh M, Macina R, Liu W, Pilkington G, Papkoff J (2005) The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation. Exp Cell Res 306:128–141

    Article  PubMed  CAS  Google Scholar 

  43. Salz W, Eisenberg D, Plescia J, Garlick DS, Weiss RM, Wu XR, Sun TT, Altieri DC (2005) A survivin gene signature predicts aggressive tumor behavior. Cancer Res 65:3531–3534

    Article  PubMed  CAS  Google Scholar 

  44. Sanges R, Cordero F, Calogero RA (2007) oneChannelGUI: a graphical interface to Bioconductor tools, designed for life scientists who are not familiar with R language. Bioinformatics 23:3406–3408

    Article  PubMed  CAS  Google Scholar 

  45. Santiago-Josefat B, Esselens C, Bech-Serra JJ, Arribas J (2007) Post-transcriptional up-regulation of ADAM17 upon epidermal growth factor receptor activation and in breast tumors. J Biol Chem 282:8325–8331

    Article  PubMed  CAS  Google Scholar 

  46. Simon I, Zhuo S, Corral L, Diamandis EP, Sarno MJ, Wolfert RL, Kim NW (2006) B7-h4 is a novel membrane-bound protein and a candidate serum and tissue biomarker for ovarian cancer. Cancer Res 66:1570–1575

    Article  PubMed  CAS  Google Scholar 

  47. Smyth GK (2004) Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol, Article 1

  48. Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, Nordgren H, Farmer P, Praz V, Haibe-Kains B, Desmedt C, Larsimont D, Cardoso F, Peterse H, Nuyten D, Buyse M, Van de Vijver MJ, Bergh J, Piccart M, Delorenzi M (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 98:262–272

    Article  PubMed  CAS  Google Scholar 

  49. Steel DM, Donoghue FC, O’Neill RM, Uhlar CM, Whitehead AS (1996) Expression and regulation of constitutive and acute phase serum amyloid A mRNAs in hepatic and non-hepatic cell lines. Scand J Immunol 44:493–500

    Article  PubMed  CAS  Google Scholar 

  50. Sun Y, Wang Y, Zhao J, Gu M, Giscombe R, Lefvert AK, Wang X (2006) B7-H3 and B7-H4 expression in non-small-cell lung cancer. Lung Cancer 53:143–151

    Article  PubMed  Google Scholar 

  51. Tanaka E, Hashimoto Y, Ito T, Okumura T, Kan T, Watanabe G, Imamura M, Inazawa J, Shimada Y (2005) The clinical significance of Aurora-A/STK15/BTAK expression in human esophageal squamous cell carcinoma. Clin Cancer Res 11:1827–1834

    Article  PubMed  CAS  Google Scholar 

  52. Treilleux I, Blay JY, Bendriss-Vermare N, Ray-Coquard I, Bachelot T, Guastalla JP, Bremond A, Goddard S, Pin JJ, Barthelemy-Dubois C, Lebecque S (2004) Dendritic cell infiltration and prognosis of early stage breast cancer. Clin Cancer Res 10:7466–7474

    Article  PubMed  CAS  Google Scholar 

  53. Tringler B, Zhuo S, Pilkington G, Torkko KC, Singh M, Lucia MS, Heinz DE, Papkoff J, Shroyer KR (2005) B7-h4 is highly expressed in ductal and lobular breast cancer. Clin Cancer Res 11:1842–1848

    Article  PubMed  CAS  Google Scholar 

  54. Turashvili G, Bouchal J, Baumforth K, Wei W, Dziechciarkova M, Ehrmann J, Klein J, Fridman E, Skarda J, Srovnal J, Hajduch M, Murray P, Kolar Z (2007) Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis. BMC Cancer 7:55

    Article  PubMed  CAS  Google Scholar 

  55. Urieli-Shoval S, Linke RP, Matzner Y (2000) Expression and function of serum amyloid A, a major acute-phase protein, in normal and disease states. Curr Opin Hematol 7:64–69

    Article  PubMed  CAS  Google Scholar 

  56. Vachani A, Nebozhyn M, Singhal S, Alila L, Wakeam E, Muschel R, Powell CA, Gaffney P, Singh B, Brose MS, Litzky LA, Kucharczuk J, Kaiser LR, Marron JS, Showe MK, Albelda SM, Showe LC (2007) A 10-gene classifier for distinguishing head and neck squamous cell carcinoma and lung squamous cell carcinoma. Clin Cancer Res 13:2905–2915

    Article  PubMed  CAS  Google Scholar 

  57. Westfall P, Krishen A, Young SS (1998) Using prior information to allocate significance levels for multiple endpoints. Stat Med 17:2107–2119

    Article  PubMed  CAS  Google Scholar 

  58. Wilson KS, Roberts H, Leek R, Harris AL, Geradts J (2002) Differential gene expression patterns in HER2/neu-positive and -negative breast cancer cell lines and tissues. Am J Pathol 161:1171–1185

    PubMed  CAS  Google Scholar 

  59. Wu Q, Parry G (2007) Hepsin and prostate cancer. Front Biosci 12:5052–5059

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from Italian Association for Cancer Research; the Italian Ministero dell’Università e della Ricerca; the University of Torino; the Compagnia di San Paolo, Torino; the Fondazione Denegri, Torino; the Fondazione Internazionale di Ricerca in Medicina Sperimentale (FIRMS), Torino; the Regione Piemonte; and Nordic Centre of Excellence for development of anti tumor Vaccine concepts (NCEV). We thank Prof. John Iliffe for critical reading of the manuscript.

Author information

Authors and Affiliations

  1. Molecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Turin, 10126, Turin, Italy

    Raffaele Adolfo Calogero, Elena Quaglino, Silvia Saviozzi, Guido Forni & Federica Cavallo

Authors
  1. Raffaele Adolfo Calogero
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elena Quaglino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Silvia Saviozzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guido Forni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Federica Cavallo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Federica Cavallo.

Additional information

This article is a symposium paper from the conference “Progress in vaccination against cancer 2007 (PIVAC 7)”, held in Stockholm, Sweden, on 10–11 September 2007.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary table: Normal tissues from GSE7307 used for POAs screening (PDF 83 kb)

262_2008_481_MOESM2_ESM.pdf

Supplementary information figure: Hierachical clustering Of Pawitan (GSE1456) and Sotirou (GSE2990) data set. The expression of 71 probe sets associated to the 46 top ranked POAs was regularized with respect to the median value of each probe set (gene median centering) and grouped by hierachical clustering (left panels). Specimens can be grouped in two main clusters (i.e. red cluster characterized by an overall higher expression with respect to the green cluster). Kaplan-Meyer analysis (right panels) on those two clusters shows a statistically significant association between reduced survival rate and high expression of the POAs. (PDF 151 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Calogero, R.A., Quaglino, E., Saviozzi, S. et al. Oncoantigens as anti-tumor vaccination targets: the chance of a lucky strike?. Cancer Immunol Immunother 57, 1685–1694 (2008). https://doi.org/10.1007/s00262-008-0481-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-008-0481-x

Keywords

Search

Navigation