Skip to main content

Therapeutic Vaccination for the Treatment of Malignant Melanoma

  • Chapter

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 176))

Abstract

With increasing knowledge of tumor-associated antigens and T cell epitopes, and the mechanisms of induction and regulation of T-cellular immune responses, therapeutic vaccination is increasingly being explored as a treatment option for cancer. Several clinical cancer vaccination trials, the majority of them with melanoma patients, have demonstrated efficient induction of tumor-specific cellular immune responses in patients. However, these immune responses, in most cases, do not translate into clinical responses. The clinical response rates in these trials are relatively low. The most likely causes for the lack of correlation of immunological and clinical responsiveness are loss of antigenicity and immune suppression. Nonetheless, many patients in the vaccination trials have experienced extended survival compared to clinical experience. Therapeutic vaccination thus appears suited for maintenance therapy where cure is not possible and is an interesting option for adjuvant therapy after surgical tumor resection. While the clinical efficacy of vaccination is expected to be better for early-stage cancer, advancement of the treatment of advanced-stage disease will require combination with other therapeutic principles.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ahmadzadeh M, Rosenberg SA (2005a) IL-2 administration increases CD4+CD25hiFoxp3+ regulatory T cells in cancer patients. Blood 107:2409–2414

    Article  PubMed  CAS  Google Scholar 

  • Ahmadzadeh M, Rosenberg SA (2005b) TGF-beta 1 attenuates the acquisition and expression of effector function by tumor antigen-specific human memory CD8 T cells. J Immunol 174:5215–5223

    PubMed  CAS  Google Scholar 

  • Antony PA, Piccirillo CA, Akpinarli A, Finkelstein SE, Speiss PJ, Surman DR, Palmer DC, Chan CC, Klebanoff CA, Overwijk WW, Rosenberg SA, Restifo NP (2005) CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. J Immunol 174:2591–2601

    PubMed  CAS  Google Scholar 

  • Boon T, Van den Eynde B (2003) Tumour immunology. Curr Opin Immunol 15:129–130

    Article  PubMed  CAS  Google Scholar 

  • Boon T, Coulie PG, Van den Eynde BJ, Van der Bruggen P (2006) Human T cell responses against melanoma. Annu Rev Immunol 24:175–208

    Article  PubMed  CAS  Google Scholar 

  • Bredenbeck A, Losch FO, Sharav T, Eichler-Mertens M, Filter M, Givehchi A, Sterry W, Wrede P, Walden P (2005) Identification of noncanonical melanoma-associated T cell epitopes for cancer immunotherapy. J Immunol 174:6716–6724

    PubMed  CAS  Google Scholar 

  • Chianese-Bullock KA, Woodson EM, Tao H, Boerner SA, Smolkin M, Grosh WW, Neese PY, Merrill P, Petroni GR, Slingluff CL Jr (2005) Autoimmune toxicities associated with the administration of antitumor vaccines and low-dose interleukin-2. J Immunother 28:412–419

    Article  PubMed  CAS  Google Scholar 

  • Demine R, Walden P (2005) Testing the role of gp96 as peptide chaperone in antigen processing. J Biol Chem 280:17573–17578

    Article  PubMed  CAS  Google Scholar 

  • Demine R, Sherev T, Walden P (2003) Biochemical determination of natural tumor-associated T-cell epitopes. Mol Biotechnol 25:71–78

    Article  PubMed  CAS  Google Scholar 

  • Ernstoff MS (2005) Self-recognition and tumor response to immunotherapy. J Clin Oncol 23:5875–5877

    Article  PubMed  Google Scholar 

  • Faries MB, Morton DL (2005) Therapeutic vaccines for melanoma: current status. BioDrugs 19:247–260

    Article  PubMed  CAS  Google Scholar 

  • Filter M, Eichler-Mertens M, Bredenbeck A, Losch FO, Sherev T, Givehchi A, Sterry W, Walden P, Wrede P (2006) A novel artificial neural network-based algorithm for the prediction of canonical and non-canonical MHC-I binding epitopes. QSAR 25:350–358

    Article  CAS  Google Scholar 

  • Habib NA (2000) Cancer gene therapy. Adv Exp Med Biol 7:456–465

    Google Scholar 

  • Hemmi H, Akira S (2005) TLR signalling and the function of dendritic cells. Chem Immunol Allergy 86:120–135

    PubMed  CAS  Google Scholar 

  • Javia LR, Rosenberg SA (2003) CD4+CD25+ suppressor lymphocytes in the circulation of patients immunized against melanoma antigens. J Immunother 26:85–93

    Article  PubMed  CAS  Google Scholar 

  • Kao JY, Zhang M, Chen CM, Chen JJ (2005) Superior efficacy of dendritic cell-tumor fusion vaccine compared with tumor lysate-pulsed dendritic cell vaccine in colon cancer. Immunol Lett 101:154–159

    Article  PubMed  CAS  Google Scholar 

  • Kaufmann SHE (1996) Concepts in vaccine development. Walter de Gruyter, Berlin

    Google Scholar 

  • Linnemann T, Wiesmuller KH, Gellrich S, Kaltoft K, Sterry W, Walden P (2000) A T-cell epitope determined with random peptide libraries and combinatorial peptide chemistry stimulates T cells specific for cutaneous T-cell lymphoma. Ann Oncol 11[Suppl 1]:95–99

    Article  PubMed  Google Scholar 

  • Linnemann T, Tumenjargal S, Gellrich S, Wiesmuller K, Kaltoft K, Sterry W, Walden P (2001) Mimotopes for tumor-specific T lymphocytes in human cancer determined with combinatorial peptide libraries. Eur J Immunol 31:156–165

    Article  PubMed  CAS  Google Scholar 

  • Lustgarten J, Dominguez AL, Pinilla C (2006) Identification of cross-reactive peptides using combinatorial libraries circumvents tolerance against Her-2/neu-immunodominant epitope. J Immunol 176:1796–1805

    PubMed  CAS  Google Scholar 

  • Novellino L, Castelli C, Parmiani G (2005) A listing of human tumor antigens recognized by T cells: March 2004 update. Cancer Immunol Immunother 54:187–207

    Article  PubMed  CAS  Google Scholar 

  • Parkhurst MR, DePan C, Riley JP, Rosenberg SA, Shu S (2003) Hybrids of dendritic cells and tumor cells generated by electrofusion simultaneously present immunodominant epitopes from multiple human tumor-associated antigens in the context of MHC class I and class II molecules. J Immunol 170:5317–5325

    PubMed  CAS  Google Scholar 

  • Parmiani G (2005) Tumor-infiltrating T cells—friend or foe of neoplastic cells? N Engl J Med 353:2640–2641

    Article  PubMed  Google Scholar 

  • Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S (1999) SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 50:213–219

    Article  PubMed  CAS  Google Scholar 

  • Riker AI, Jove R, Daud AI (2006) Immunotherapy as part of a multidisciplinary approach to melanoma treatment. Front Biosci 11:1–14

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg SA (2005a) Cancer immunotherapy comes of age. Nat Clin Pract Oncol 2:115

    Article  PubMed  Google Scholar 

  • Rosenberg SA (2005b) The emergence of modern cancer immunotherapy. Ann Surg Oncol 12:344–346

    Article  PubMed  Google Scholar 

  • Rosenberg SA, Sherry RM, Morton KE, Scharfman WJ, Yang JC, Topalian SL, Royal RE, Kammula U, Restifo NP, Hughes MS, Schwartzentruber D, Berman DM, Schwarz SL, Ngo LT, Mavroukakis SA, White DE, Steinberg SM (2005) Tumor progression can occur despite the induction of very high levels of self/tumor antigen-specific CD8+ T cells in patients with melanoma. J Immunol 175:6169–6176

    PubMed  CAS  Google Scholar 

  • Salcedo M, Bercovici N, Taylor R, Vereecken P, Massicard S, Duriau D, Vernel-Pauillac F, Boyer A, Baron-Bodo V, Mallard E, Bartholeyns J, Goxe B, Latour N, Leroy S, Prigent D, Martiat P, Sales F, Laporte M, Bruyns C, Romet-Lemonne JL, Abastado JP, Lehmann F, Velu T (2005) Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate. Cancer Immunol Immunother 54:1–11

    Article  CAS  Google Scholar 

  • Schuler G, Schuler-Thurner B, Steinman RM (2003) The use of dendritic cells in cancer immunotherapy. Curr Opin Immunol 2003 15:138–147

    Article  PubMed  CAS  Google Scholar 

  • Sherev T, Wiesmuller KH, Walden P (2003) Mimotopes of tumor-associated T-cell epitopes for cancer vaccines determined with combinatorial peptide libraries. Mol Biotechnol 25:53–61

    Article  PubMed  CAS  Google Scholar 

  • Stuhler G, Walden P (1993) Collaboration of helper and cytotoxic T lymphocytes. Eur J Immunol 23:2279–2286

    Article  PubMed  CAS  Google Scholar 

  • Stuhler G, Walden P (1994) Recruitment of helper T cells for induction of tumour rejection by cytolytic T lymphocytes. Cancer Immunol Immunother 39:342–345

    PubMed  CAS  Google Scholar 

  • Stuhler G, Walden P (2002) Cancer immune therapy. Wiley-VCH, Weinheim

    Google Scholar 

  • Tagawa ST, Cheung E, Banta W, Gee C, Weber JS (2006) Survival analysis after resection of metastatic disease followed by peptide vaccines in patients with Stage IV melanoma. Cancer 106:1353–1357

    Article  PubMed  Google Scholar 

  • Trefzer U, Walden P (2003) Hybrid cell vaccines for cancer immune therapy. Mol Biotechnol 25:63–70

    Article  PubMed  CAS  Google Scholar 

  • Trefzer U, Weingart G, Chen Y, Herberth G, Adrian K, Winter H, Audring H, Guo Y, Sterry W, Walden P (2000) Hybrid cell vaccination for cancer immune therapy: first clinical trial with metastatic melanoma. Int J Cancer 85:618–626

    Article  PubMed  CAS  Google Scholar 

  • Trefzer U, Herberth G, Wohlan K, Milling A, Thiemann M, Sherev T, Sparbier K, Sterry W, Walden P (2004) Vaccination with hybrids of tumor and dendritic cells induces tumor-specific T-cell and clinical responses in melanoma stage III and IV patients. Int J Cancer 110:730–740

    Article  PubMed  CAS  Google Scholar 

  • Trefzer U, Herberth G, Wohlan K, Milling A, Thiemann M, Sharav T, Sparbier K, Sterry W, Walden P (2005) Tumour-dendritic hybrid cell vaccination for the treatment of patients with malignant melanoma: immunological effects and clinical results. Vaccine 23:2367–2373

    Article  PubMed  CAS  Google Scholar 

  • Tumenjargal S, Gellrich S, Linnemann T, Muche JM, Lukowsky A, Audring H, Wiesmuller KH, Sterry W, Walden P (2003) Anti-tumor immune responses and tumor regression induced with mimotopes of a tumor-associated T cell epitope. Eur J Immunol 33:3175–3185

    Article  PubMed  CAS  Google Scholar 

  • van der Bruggen P, Van den Eynde BJ (2006) Processing and presentation of tumor antigens and vaccination strategies. Curr Opin Immunol 18:98–104

    Article  PubMed  CAS  Google Scholar 

  • Van Der Bruggen P, Zhang Y, Chaux P, Stroobant V, Panichelli C, Schultz ES, Chapiro J, Van Den Eynde BJ, Brasseur F, Boon T (2002) Tumor-specific shared antigenic peptides recognized by human T cells. Immunol Rev 188:51–64

    Article  Google Scholar 

  • Walden P (2000) Hybrid cell vaccination for cancer immunotherapy. Adv Exp Med Biol 465:347–354

    Article  PubMed  CAS  Google Scholar 

  • Walden P, Sterry W (2004) New and emerging vaccination strategies for prevention and treatment of dermatological diseases. Expert Rev Vaccines 3:421–431

    Article  PubMed  CAS  Google Scholar 

  • Whiteside TL (2000) Monitoring of antigen-specific cytolytic T lymphocytes in cancer patients receiving immunotherapy. Clin Diagn Lab Immunol 7:327–332

    Article  PubMed  CAS  Google Scholar 

  • Whiteside TL (2004) Methods to monitor immune response and quality control. Dev Biol (Basel) 116:219–228

    CAS  Google Scholar 

  • Whiteside TL (2006) Immune suppression in cancer: effects on immune cells, mechanisms and future therapeutic intervention. Semin Cancer Biol 16:3–15

    Article  PubMed  CAS  Google Scholar 

  • Whiteside TL, Odoux C (2004) Dendritic cell biology and cancer therapy. Cancer Immunol Immunother 53:240–248

    Article  PubMed  Google Scholar 

  • Whiteside TL, Zhao Y, Tsukishiro T, Elder EM, Gooding W, Baar J (2003) Enzyme-linked immunospot, cytokine flow cytometry, and tetramers in the detection of T-cell responses to a dendritic cell-based multipeptide vaccine in patients with melanoma. Clin Cancer Res 9:641–649

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Walden, P. (2007). Therapeutic Vaccination for the Treatment of Malignant Melanoma. In: Dietel, M. (eds) Targeted Therapies in Cancer. Recent Results in Cancer Research, vol 176. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-46091-6_19

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-46091-6_19

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-46090-9

  • Online ISBN: 978-3-540-46091-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics