Skip to main content

Advertisement

SpringerLink
Log in

High-molecular-weight melanoma-associated antigen mimotope immunizations induce antibodies recognizing melanoma cells

  • Original Article
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Size and posttranslational modifications are obstacles in the recombinant expression of high-molecular-weight melanoma-associated antigen (HMW-MAA). Creating a tumor antigen mimic via the phage display technology may be a means to overcome this problem for vaccine design. In this study, we aimed to generate an immunogenic epitope mimic of HMW-MAA. Therefore we screened a linear 9mer phage display peptide library, using the anti-HMW-MAA monoclonal antibody (mAb) 225.28S. This antibody mediates antibody-dependent cellular cytotoxicity (ADCC) and has already been used for anti-idiotype therapy trials. Fifteen peptides were selected by mAb 225.28S in the biopanning procedure. They share a consensus sequence, but show only partial homology to the amino acid sequence of the HMW-MAA core protein, indicating mimicry with a conformational epitope. One mimotope was chosen to be fused to albumin binding protein (ABP) as an immunogenic carrier. Immunoassays with 225.28S indicated that the mimotope fusion protein was folded correctly. Subsequently, the fusion protein was tested for immunogenicity in BALB/c mice. The induced anti-mimotope antibodies recognized HMW-MAA of 518A2 human melanoma cells, whereas sera of mice immunized with the carrier ABP alone showed no reactivity. These anti-mimotope antibodies were capable of inducing specific lysis of 518A2 melanoma cells in ADCC assays with murine effector cells. In conclusion, the presented data indicate that mimotopes fused to an immunogenic carrier are suitable tools to elicit epitope-specific anti-melanoma immune responses.

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
Fig. 5

Similar content being viewed by others

References

  1. Natali PG, Imai K, Wilson BS, Bigotti A, Cavaliere R, Pellegrino MA, Ferrone S (1981) Structural properties and tissue distribution of the antigen recognized by the monoclonal antibody 653.40S to human melanoma cells. J Natl Cancer Inst 67:591–601

    CAS  PubMed  Google Scholar 

  2. Schlingemann RO, Rietveld FJ, de Waal RM, Ferrone S, Ruiter DJ (1990) Expression of the high molecular weight melanoma-associated antigen by pericytes during angiogenesis in tumors and in healing wounds. Am J Pathol 136:1393–1405

    CAS  PubMed  Google Scholar 

  3. Buraggi GL (1986) Radioimmunodetection of malignant melanoma with the 225.28S monoclonal antibody to HMW-MAA. Nuklearmedizin 25:220–224

    CAS  PubMed  Google Scholar 

  4. Bender H, Grapow M, Schomburg A, Reinhold U, Biersack HJ (1997) Effects of diagnostic application of monoclonal antibody on survival in melanoma patients. Hybridoma 16:65–68

    CAS  PubMed  Google Scholar 

  5. Mittelman A, Chen ZJ, Liu CC, Hirai S, Ferrone S (1994) Kinetics of the immune response and regression of metastatic lesions following development of humoral anti-high molecular weight-melanoma associated antigen immunity in three patients with advanced malignant melanoma immunized with mouse antiidiotypic monoclonal antibody MK2-23. Cancer Res 54:415–421

    CAS  PubMed  Google Scholar 

  6. Klinger M, Kudlacek O, Seidel MG, Freissmuth M, Sexl V (2002) MAP kinase stimulation by cAMP does not require RAP1 but SRC family kinases. J Biol Chem 277:32490–32497

    Article  CAS  PubMed  Google Scholar 

  7. Imai K, Molinaro GA, Ferrone S (1980) Monoclonal antibodies to human melanoma-associated antigens. Transplant Proc 12:380–383

    CAS  PubMed  Google Scholar 

  8. Wilson BS, Imai K, Natali PG, Ferrone S (1981) Distribution and molecular characterization of a cell-surface and a cytoplasmic antigen detectable in human melanoma cells with monoclonal antibodies. Int J Cancer 28:293–300

    CAS  PubMed  Google Scholar 

  9. Felici F, Luzzago A, Folgori A, Cortese R (1993) Mimicking of discontinuous epitopes by phage-displayed peptides, II. Selection of clones recognized by a protective monoclonal antibody against the Bordetella pertussis toxin from phage peptide libraries. Gene 128:21–27

    Article  CAS  PubMed  Google Scholar 

  10. Parmley SF, Smith GP (1988) Antibody-selectable filamentous fd phage vectors: affinity purification of target genes. Gene 73:305–318

    Article  CAS  PubMed  Google Scholar 

  11. Barbas CF III, Lerner RA (1991) Combinatorial immunoglobulin libraries on the surface of phage (phabs): rapid selection of antigen-specific Fabs. In: Methods: a companion to methods in enzymology. Academic, New York, pp 119–24

  12. Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467

    CAS  PubMed  Google Scholar 

  13. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680

    CAS  PubMed  Google Scholar 

  14. Baumann S, Grob P, Stuart F, Pertlik D, Ackermann M, Suter M (1998) Indirect immobilization of recombinant proteins to a solid phase using the albumin binding domain of streptococcal protein G and immobilized albumin. J Immunol Methods 221:95–106

    Article  CAS  PubMed  Google Scholar 

  15. Krebber A, Bornhauser S, Burmester J, Honegger A, Willuda J, Bosshard HR, Pluckthun A (1997) Reliable cloning of functional antibody variable domains from hybridomas and spleen cell repertoires employing a reengineered phage display system. J Immunol Methods 201:35–55

    Article  CAS  PubMed  Google Scholar 

  16. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    PubMed  Google Scholar 

  17. Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76:4350–4354

    CAS  PubMed  Google Scholar 

  18. Ravetch JV, Kinet JP (1991) Fc receptors. Annu Rev Immunol 9:457–492

    CAS  PubMed  Google Scholar 

  19. Riemer AB, Klinger M, Wagner S, Bernhaus A, Mazzucchelli L, Pehamberger H, Scheiner O, Zielinski CC, Jensen-Jarolim E (2004) Generation of peptide mimics of the epitope recognized by trastuzumab on the oncogenic protein Her-2/neu. J Immunol 173:394–401

    CAS  PubMed  Google Scholar 

  20. Yip YL, Smith G, Koch J, Dubel S, Ward RL (2001) Identification of epitope regions recognized by tumor inhibitory and stimulatory anti-ErbB-2 monoclonal antibodies: implications for vaccine design. J Immunol 166:5271–5278

    CAS  PubMed  Google Scholar 

  21. Ferrone S, Wang X (2001) Active specific immunotherapy of malignant melanoma and peptide mimics of the human high-molecular-weight melanoma-associated antigen. Recent Results Cancer Res 158:231–235

    CAS  PubMed  Google Scholar 

  22. Garrigues HJ, Lark MW, Lara S, Hellstrom I, Hellstrom KE, Wight TN (1986) The melanoma proteoglycan: restricted expression on microspikes, a specific microdomain of the cell surface. J Cell Biol 103:1699–1710

    Article  CAS  PubMed  Google Scholar 

  23. Eisenmann KM, McCarthy JB, Simpson MA, Keely PJ, Guan JL, Tachibana K, Lim L, Manser E, Furcht LT, Iida J (1999) Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas. Nat Cell Biol 1:507–513

    Article  CAS  PubMed  Google Scholar 

  24. Meola A, Delmastro P, Monaci P, Luzzago A, Nicosia A, Felici F, Cortese R, Galfre G (1995) Derivation of vaccines from mimotopes. Immunologic properties of human hepatitis B virus surface antigen mimotopes displayed on filamentous phage. J Immunol 154:3162–3172

    CAS  PubMed  Google Scholar 

  25. Schöll I, Wiedermann U, Forster-Waldl E, Ganglberger E, Baier K, Boltz-Nitulescu G, Scheiner O, Ebner C, Jensen-Jarolim E (2002) Phage-displayed Bet mim 1, a mimotope of the major birch pollen allergen Bet v 1, induces B cell responses to the natural antigen using bystander T cell help. Clin Exp Allergy 32:1583–1588

    Article  PubMed  Google Scholar 

  26. Jensen-Jarolim E, Leitner A, Kalchhauser H, Zurcher A, Ganglberger E, Bohle B, Scheiner O, Boltz-Nitulescu G, Breiteneder H (1998) Peptide mimotopes displayed by phage inhibit antibody binding to bet v 1, the major birch pollen allergen, and induce specific IgG response in mice. FASEB J 12:1635–1642

    CAS  PubMed  Google Scholar 

  27. Partidos CD (2000) Peptide mimotopes as candidate vaccines. Curr Opin Mol Ther 2:74–79

    CAS  PubMed  Google Scholar 

  28. Ganglberger E, Sponer B, Scholl I, Wiedermann U, Baumann S, Hafner C, Breiteneder H, Suter M, Boltz-Nitulescu G, Scheiner O, Jensen-Jarolim E (2001) Monovalent fusion proteins of IgE mimotopes are safe for therapy of type I allergy. FASEB J 15:2524–2526

    CAS  PubMed  Google Scholar 

  29. Hantusch B, Untersmayr E, Schöll I, Krieger S, Wiedermann U, Ganglberger E, Suter M, Boltz-Nitulescu G, Scheiner O, Jensen-Jarolim E (2004) IgE-mimotopes are safe for immunizations when displayed in a monovalent manner. In: Allergy Frontiers and Futures, Bienenstock JB, Ring S, Togias AG (eds) Proceedings of the 24th Symposium of the Collegium Internationale Allergologicum: 292–297

  30. Chattopadhyay P, Kaveri SV, Byars N, Starkey J, Ferrone S, Raychaudhuri S (1991) Human high molecular weight-melanoma associated antigen mimicry by an anti-idiotypic antibody: characterization of the immunogenicity and the immune response to the mouse monoclonal antibody IMel-1. Cancer Res 51:6045–6051

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Magdolna Vermes and Harald Kurz for excellent technical assistance. This work was supported by BioLife Science GmbH, Vienna, Austria, and by a grant of the Austrian National Bank, OeNB 8301. B. Hantusch was supported by grant P14339-B13 of the Austrian Science Fund.

Author information

Authors and Affiliations

  1. Department of Pathophysiology, Center of Physiology & Pathophysiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria

    Angelika B. Riemer, Brigitte Hantusch, Barbara Sponer, Georg Kraml, Christine Hafner, Otto Scheiner & Erika Jensen-Jarolim

  2. BioLife Science GmbH, Vienna, Austria

    Angelika B. Riemer, Christoph C. Zielinski, Otto Scheiner, Hubert Pehamberger & Erika Jensen-Jarolim

  3. Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria

    Christoph C. Zielinski

  4. Department of Dermatology, Medical University of Vienna, Vienna, Austria

    Hubert Pehamberger

Authors
  1. Angelika B. Riemer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brigitte Hantusch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Barbara Sponer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Georg Kraml
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christine Hafner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christoph C. Zielinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Otto Scheiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hubert Pehamberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Erika Jensen-Jarolim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erika Jensen-Jarolim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Riemer, A.B., Hantusch, B., Sponer, B. et al. High-molecular-weight melanoma-associated antigen mimotope immunizations induce antibodies recognizing melanoma cells. Cancer Immunol Immunother 54, 677–684 (2005). https://doi.org/10.1007/s00262-004-0632-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-004-0632-7

Keywords

Search

Navigation