Cancer Immunology, Immunotherapy

, Volume 61, Issue 4, pp 581–585 | Cite as

The entirely carbohydrate immunogen Tn-PS A1 induces a cancer cell selective immune response and cytokine IL-17

  • Ravindra A. De Silva
  • Dananjaya K. Appulage
  • Halina Pietraszkiewicz
  • Kevin R. Bobbitt
  • Joe Media
  • JiaJiu Shaw
  • Fred A. Valeriote
  • Peter R. AndreanaEmail author
Short Communication


The tumor-associated carbohydrate antigen/hapten Thomsen-nouveau (Tn; α-D-GalpNAc-ONH2) was conjugated to a zwitterionic capsular polysaccharide, PS A1, from commensal anaerobe Bacteroides fragilis ATCC 25285/NCTC 9343 for the development of an entirely carbohydrate cancer vaccine construct and probed for immunogenicity. This communication discloses that murine anti-Tn IgG3 antibodies both bind to and recognize human tumor cells that display the Tn hapten. Furthermore, the sera from immunization of mice with Tn-PS A1 contain cytokine interleukin 17 (IL-17A), which is known to possess anti-tumor function and represents a striking difference to an IL-2, and IL-6 profile obtained with anti-PS A1 sera.


Carbohydrates Antigen Tumor Vaccine Interleukin 17 Flow cytometry 



Authors thank Dr. Mary Kay Pflum for Jurkat and JurkatTAg cell lines. P.R.A acknowledges Wayne State University for financial support and the National Institutes of Health/National Cancer Institute for an R01 CA 156661 award.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Avery OT, Goebel WF (1929) Chemo-immunological studies on conjugated carbohydrate-proteins: II. Immunological specificity of synthetic sugar-protein antigens. J Exp Med 50:533–550PubMedCrossRefGoogle Scholar
  2. 2.
    Landsteiner K, van der Scheer J (1927) On the influence of acid groups on the serological specificity of azoproteins. J Exp Med 45:1045–1056PubMedCrossRefGoogle Scholar
  3. 3.
    Astronomo RD, Burton DR (2010) Carbohydrate vaccines: developing sweet solutions to sticky situations? Nat Rev Drug Discov 9:308–324PubMedCrossRefGoogle Scholar
  4. 4.
    Galonic DP, Gin DY (2007) Chemical glycosylation in the synthesis of glycoconjugate antitumor vaccines. Nature 446:1000–1007PubMedCrossRefGoogle Scholar
  5. 5.
    Velez CD, Lewis CJ, Kasper DL, Cobb BA (2009) Type I streptococcus pneumonia carbohydrate utilizes a nitric oxide and MHC II-dependent pathway for antigen presentation immunology 127:73–82Google Scholar
  6. 6.
    Esplugues E et al (2011) Control of TH17 cells occurs in the small intestine. Nature 475:514–518PubMedCrossRefGoogle Scholar
  7. 7.
    Jegerlehner A et al (2010) Carrier induced epitomic suppression of antibody responses induced by virus-like particles is a dynamic phenomenon caused by carrier-specific antibodies. Vaccine 28:5503–5512PubMedCrossRefGoogle Scholar
  8. 8.
    Zijlstra A, Testa JE, Quigley JP (2003) Targeting the proteome/epitome, implementation of subtractive immunization. Biochem Biophys Res Commun 303:733–744PubMedCrossRefGoogle Scholar
  9. 9.
    Cobb BA, Wang Q, Tzianabos AO, Kasper DL (2004) Polysaccharide processing and presentation by the MHCII pathway. Cell 117:677–687PubMedCrossRefGoogle Scholar
  10. 10.
    De Silva RA, Wang Q, Chidley T, Appulage DK, Andreana PR (2009) Immunological responses from an entirely carbohydrate antigen: design of synthetic vaccines based on Tn-PS A1 conjugates. J Am Chem Soc 131:9622–9623PubMedCrossRefGoogle Scholar
  11. 11.
    Markham RB, Pier GB, Schreiber JR (1991) The role of cytophilic IgG3 antibody in T cell-mediated resistance to infection with the extracellular bacterium, Pseudomonas aeruginosa. J Immunol 146:316–320PubMedGoogle Scholar
  12. 12.
    Perlmutter RM, Hansburg D, Briles DE, Nicolotti RA, Davie JM (1978) Subclass restriction of murine anti-carbohydrate antibodies. J Immunol 121:566–572PubMedGoogle Scholar
  13. 13.
    Azeredo da Silveira S et al (2002) Complement activation selectively potentiates the pathogenicity of the IgG2b and IgG3 isotypes of a high affinity anti-erythrocyte autoantibody. J Exp Med 195:665–672PubMedCrossRefGoogle Scholar
  14. 14.
    An Z (2009) Therapeutic monoclonal antibodies: from bench to clinic, Ch 16. Wiley, New JerseyGoogle Scholar
  15. 15.
    Carcel-Trullols J (2006) Characterization of the glycosylation profile of the human breast cancer cell line, MDA-231, and a bone colonizing variant. Int J Oncol 28:1173–1183PubMedGoogle Scholar
  16. 16.
    Fernsten P, Shaw M, Hocker S, Fulghum R, Winfield J (1998) Expression of the sialosyl-Tn epitope on CD45 derived from activated peripheral blood T cells. Immunol Invest 27:323–338PubMedCrossRefGoogle Scholar
  17. 17.
    Thurnher M, Rusconi S, Berger EG (1993) Persistent repression of a functional allele can be responsible for galactosyltransferase deficiency in Tn syndrome. J Clin Invest 91:2103–2110PubMedCrossRefGoogle Scholar
  18. 18.
    Suzuki M et al (2005) Polysialic acid facilitates tumor invasion by glioma cells. Glycobiology 15:887–894PubMedCrossRefGoogle Scholar
  19. 19.
    Mazmanian SK, Round JL, Kasper DL (2008) A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453:620–625PubMedCrossRefGoogle Scholar
  20. 20.
    Chung DR et al (2003) CD4+ T cells mediate abscess formation in intra-abdominal sepsis by an IL-17-dependent mechanism. J Immunol 170:1958–1963PubMedGoogle Scholar
  21. 21.
    Michel ML et al (2008) Critical role of ROR-γt in a new thymic pathway leading to IL-17-producing invariant NKT cell differentiation. Proc Natl Acad Sci USA 105:19845–19850PubMedCrossRefGoogle Scholar
  22. 22.
    Ness-Schwickerath KJ, Morita CT (2011) Regulation and function of IL-17A- and IL-22-producing γδ T cells. Cell Mol Life Sci 68:2371–2390PubMedCrossRefGoogle Scholar
  23. 23.
    Da Silva CA, Hartl D, Liu W, Lee GL, Elias JA (2008) TLR-2 and IL-17A in chitin-induced macrophage activation and acute inflammation. J Immunol 181:4279–4286PubMedGoogle Scholar
  24. 24.
    Muranski P et al (2008) Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood 112:362–373PubMedCrossRefGoogle Scholar
  25. 25.
    Benchetrit F et al (2002) Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism. Blood 99:2114–2121PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Ravindra A. De Silva
    • 1
  • Dananjaya K. Appulage
    • 1
  • Halina Pietraszkiewicz
    • 2
    • 3
  • Kevin R. Bobbitt
    • 4
  • Joe Media
    • 2
    • 3
  • JiaJiu Shaw
    • 5
  • Fred A. Valeriote
    • 2
    • 3
  • Peter R. Andreana
    • 1
    Email author
  1. 1.Department of ChemistryWayne State UniversityDetroitUSA
  2. 2.Division of Hematology and Oncology, Department of Internal MedicineHenry Ford Health SystemDetroitUSA
  3. 3.The Josephine Ford Cancer CenterDetroitUSA
  4. 4.Department of Public Health Sciences Henry Ford HospitalDetroitUSA
  5. 5.21st Century Therapeutics, Inc.DetroitUSA

Personalised recommendations