Skip to main content
SpringerLink
Log in

Therapeutic Cancer Vaccines for Melanoma

  • Chapter
  • First Online:
Melanoma

  • 1651 Accesses

Abstract

Melanoma has long been a prominent focus of investigation for cancer immunotherapy due to its intrinsically immunogenic nature, typically a consequence of a high mutational load. Furthermore, tumor infiltration by lymphocytes provides evidence of endogenous immune activity, as does the spontaneous regression described in some tumors. Conversely, the melanoma microenvironment promotes upregulation of immunosuppressive cells (myeloid-derived suppressor cells and regulatory T cells) and cytokines (such as IL-6, IL-10, TNFα, TGFβ, and VEGF) facilitating evasion of the immune response. The tumor microenvironment contains several targets for immunomodulation that are under active investigation. In this chapter, we will explore the development of immunotherapy for the treatment of melanoma, beginning with early, nonspecific immunomodulation through more recent advances in melanoma vaccines with specific discussion of several phase III clinical trials for peptide, viral, dendritic cell, and whole tumor cell-based vaccines.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
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

Institutional subscriptions

References

  1. Coley WB. The treatment of inoperable sarcoma by bacterial toxins (the mixed toxins of the streptococcus erysipelas and the Bacillus prodigiosus). Proc R Soc Med. 1910;3(Surg Sect):1–48.

    PubMed  PubMed Central  CAS  Google Scholar 

  2. Foley EJ. Antigenic properties of Methylcholanthrene-induced tumors in mice of the strain of origin. Cancer Res. 1953;13:835.

    PubMed  CAS  Google Scholar 

  3. Prehn RT, Main JM. Immunity to Methylcholanthrene-induced sarcomas. J Nat Cancer Inst. 1957;18:769.

    PubMed  CAS  Google Scholar 

  4. Morton DL, Malmgren RA, Holmes EC, Ketcham AS. Demonstration of antibodies against human malignant melanoma by immunofluorescence. Surgery. 1968;64:233.

    PubMed  CAS  Google Scholar 

  5. Ramirez-Montagut T, Turk MJ, Wolchok JD, Guevara-Patino JA, Houghton A. Immunity to melanoma: unraveling the relation of tumor immunity and autoimmunity. Oncogene. 2003;22:3180–7.

    Article  CAS  PubMed  Google Scholar 

  6. Morton DL, Eilber FR, Holmes EC, Hunt JS, Ketcham AS, Silverstein MJ, Sparks FC. BCG immunotherapy of malignant melanoma: summary of a seven-year experience. Ann Surg. 1974;180:635–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Agarwala SS, Neuberg D, Park Y, Kirkwood JM. Mature results of a phase III randomized trial of Bacillus Calmette–Guerin (BCG) versus observation and BCG plus Dacarbazine versus BCG in the adjuvant therapy of American joint committee on cancer stage I–III melanoma (E1673). Cancer. 2004;100:1692–8.

    Article  CAS  PubMed  Google Scholar 

  8. Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M, Paradise C, Kunkel L, Rosenberg SA. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17(7):2105–16.

    Article  CAS  Google Scholar 

  9. Byers BA, Temple-Oberle CF, Hurdle V, McKinnon JG. Treatment of in-transit melanoma with intra-lesional interleukin-2: a systematic review. J Surg Oncol. 2014;110:770–5.

    Article  CAS  PubMed  Google Scholar 

  10. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon Alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the eastern cooperative oncology group trial EST 1684. J Clin Oncol. 1996;14:7–17.

    Article  CAS  PubMed  Google Scholar 

  11. Eggermont AMM, Suciu S, Santinami M, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomized phase III trial. Lancet. 2008;372:117–26.

    Article  CAS  PubMed  Google Scholar 

  12. Rosenberg SA, Yang JC, Sherry RM, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T cell transfer immunotherapy. Clin Cancer Res. 2011;17(13):4550–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Rosenberg SA, Yannelli JR, Yang JC, et al. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst. 1994;86(15):1159–66.

    Article  CAS  PubMed  Google Scholar 

  14. Schadendorf D, Hodi FS, Robert C, et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol. 2015;33(17):1889–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30.

    Article  CAS  Google Scholar 

  16. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–32.

    Article  CAS  Google Scholar 

  17. Rosenberg SA, et al. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med. 1998;4:321–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 2011;364(22):2119–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Livingston PO, Wong GY, Adluri S, et al. Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside. J Clin Oncol. 1994;12:1036–44.

    Article  CAS  PubMed  Google Scholar 

  21. Eggermont AMM, Suciu S, Rutkowski P, et al. Adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation after resection of primary tumor >1.5 mm in patients with stage II melanoma: results of the EORTC 18961 randomized phase III trial. J Clin Oncol. 2013;31:3831–7.

    Article  CAS  PubMed  Google Scholar 

  22. Kirkwood JM, Lee S, Moschos SJ, et al. Immunogenicity and antitumor effects of vaccination with peptide vaccine +/−granulocyte-monocyte colony-stimulating factor and/or IFN-alpha2b in advanced metastatic melanoma: Eastern Cooperative Oncology Group phase II trial E1696. Clin Cancer Res. 2009;15:1443–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lawson DH, Lee S, Zhao F, et al. Randomized, placebo-controlled, phase III trial of yeast-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) versus peptide vaccination versus GM-CSF plus peptide vaccination versus placebo in patients with no evidence of disease after complete surgical resection of locally advanced and/or stage IV melanoma: a trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E4697). J Clin Oncol. 2015;33:4066–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Srivastava P. Interactions of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Ann Rev Immunol. 2002;20:395–425.

    Article  CAS  Google Scholar 

  25. Testori A, Richards J, Whitman E, Mann GB, Lutzky J, Camacho L, et al. Phase III comparison of vitespen, an autologous tumor-derived heat shock protein gp96 peptide complex vaccine, with physician's choice of treatment for stage IV melanoma: the C-100-21 Study Group. J Clin Oncol. 2008;26(6):955–62.

    Article  CAS  Google Scholar 

  26. National Institute of Health. ClinicalTrials.gov. http://clinicaltrials.gov. Accessed 31 May 2017.

  27. Bystryn JC, Zelenuch-Jacquotte A, Oratz R, Shapiro RL, Harris MN, Roses DF. Double-blind trial of a polyvalent, shed-antigen, melanoma vaccine. Clin Cancer Res. 2001;7(2001):1882–7.

    PubMed  CAS  Google Scholar 

  28. Polynoma. Prior Clinical Trials: Phase2 Studies. http://www.polynoma.com. Accessed 31 May 2017.

  29. Kruit WH, Suciu S, Dreno B, Mortier L, Robert C, Chiarion-Sileni V, et al. Selection of immunostimulant AS15 for active immunization with MAGE-A3 protein: results of a randomized phase II study of the European Organisation for Research and Treatment of Cancer melanoma Group in Metastatic Melanoma. J Clin Oncol. 2013;31(19):2413–20.

    Article  CAS  PubMed  Google Scholar 

  30. Vansteenkiste J, Zielinski M, Linder A, Dahabreh J, Gonzalez EE, Malinowski W, et al. Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase II randomized study results. J Clin Oncol. 2013;31(19):2396–403.

    Article  CAS  PubMed  Google Scholar 

  31. Hersey P, Edwards A, Coates A, et al. Evidence that treatment with vaccinia melanoma cell lysates (VMCL) may improve survival of patients with stage II melanoma. Cancer Immunol Immunother. 1897;25:257–65.

    Google Scholar 

  32. Berd D, Maquire HC, Mastrangelo MJ. Induction of cell- mediated immunity to autologous melanoma cells and regression of metastases after treatment with a melanoma cell vaccine preceded by cyclophosphamide. Cancer Res. 1986;46:2572–7.

    PubMed  CAS  Google Scholar 

  33. Hershey P, Coates AS, McCarthy WH, et al. Adjuvant immunotherapy of patients with high-risk melanoma using vaccinia viral lysates of melanoma: results of a randomized trial. J Clin Oncol. 2002;20:4181–90.

    Article  CAS  Google Scholar 

  34. Senzer NN, Kaufman HL, Amatruda T, et al. Phase II clinical trial of a granulocyte-macrophage colony- stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic mel- anoma. J Clin Oncol. 2009;27:5763–71.

    Article  CAS  PubMed  Google Scholar 

  35. Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS, Milhem M, Cranmer L, Curti B, Lewis K, Ross M, Guthrie T, Linette GP, Daniels GA, Harrington K, Middleton MR, Miller WH Jr, Zager JS, Ye Y, Yao B, Li A, Doleman S, VanderWalde A, Gansert J, Coffin RS. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33(25):2780–8.

    Article  CAS  Google Scholar 

  36. Food and Drug Administration. FDA approves first-of-its-kind product for the treatment of melanoma. http://www.fda.gov. Accessed 31 May 2017.

  37. Wilgenhof S, Corthals J, Van Nuffel AM, et al. Long-term clinical outcome of melanoma patients treated with messenger RNA-electroporated dendritic cell therapy following complete resection of metastases. Cancer Immunol Immunother. 2015;64(3):381–8.

    Article  CAS  PubMed  Google Scholar 

  38. Schuler-Thurner B, Bartz-Schmidt KU, Bornfeld N, et al. Immunotherapy of uveal melanoma: vaccination against cancer. Multicenter adjuvant phase 3 vaccination study using dendritic cells laden with tumor RNA for large newly diagnosed uveal melanoma. Ophthalmologe. 2015;112(12):1017–21.

    Article  CAS  PubMed  Google Scholar 

  39. Greene J, Hale D, Schneble E, Yu X, Nichol P, Yin S, et al.. Initial phase I/IIa trial results of an autologous tumor lysate + yeast cell wall particles + dendritic cells vaccine (TLPLDC) in patients with solid tumors. CRI-CIMT-EATI-AACR - The Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; 2015; New York, NY, USA.

    Google Scholar 

  40. Holmes LM, Li J, Sticca RP, Wagner TE, Wei Y. A rapid, novel strategy to induce tumor cell-specific cytotoxic T lymphocyte responses using instant dentritomas. J Immunother. 2001;24(2):122–9.

    Article  CAS  PubMed  Google Scholar 

  41. Greene JM, Schneble EJ, Jackson DO, et al. A phase I/IIa clinical trial in stage IV melanoma of an autologous tumor-dendritic cell fusion (dendritoma) vaccine with low dose interleukin-2. Cancer Immunol Immunother. 2016;65(4):383–92.

    Article  CAS  PubMed  Google Scholar 

  42. Mitchell MS, Kan-Mitchell J, Kempf RA, et al. Active specific immunotherapy for melanoma: phase I trial of allogeneic lysates and a novel adjuvant. Cancer Res. 1988;48:5883–93.

    PubMed  CAS  Google Scholar 

  43. Carson WE, Unger JM, Sosman JA, et al. Adjuvant vaccine immunotherapy of resected, clinically node-negative melanoma: long-term outcome and impact of HLA class I antigen expression on overall survival. Cancer Immunol Res. 2014;2(10):981–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Berd D, Maguire HC, Schuchter LM, et al. Autologous hapten-modified melanoma vaccine as postsurgical adjuvant treatement after resection of nodal metastases. J Clin Oncol. 1997;15(6):2359–70.

    Article  CAS  PubMed  Google Scholar 

  45. Berd D, Sato T, Maguire HC, et al. Immunopharmacologic analysis of an autologous, hapten-modified human melanoma vaccine. J Clin Oncol. 2004;22(3):403–15.

    Article  CAS  PubMed  Google Scholar 

  46. Morton DL, Hsueh EC, Essner R, et al. Prolonged survival of patients receiving active immunotherapy with Canvaxin therapeutic polyvalent vaccine after complete resection of melanoma metastatic to regional lymph nodes. Ann Surg. 2002;236(4):438–49.

    Article  PubMed  PubMed Central  Google Scholar 

  47. SEC Archives. CancerVax announces results of phase 3 clinical trials of Canvaxin™ in patients with stage III and stage IV melanoma. http://www.sec.gov/archives. Accessed 1 June 2017.

  48. Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369:122–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Carreno BM, Magrini V, Becker-Hapak M, et al. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 2015;348(6236):803–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General Surgery, San Antonio Military Medical Center, Fort Sam Houston, TX, USA

    Kaitlin M. Peace, Garth S. Herbert & G. Travis Clifton

  2. Department of General Surgery, Womack Army Medical Center, Ft. Bragg, NC, USA

    Timothy J. Vreeland

  3. Cancer Insight, LLC, San Antonio, TX, USA

    George E. Peoples

Authors
  1. Kaitlin M. Peace
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Garth S. Herbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Timothy J. Vreeland
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Travis Clifton
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. George E. Peoples
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Louisiana State University, New Orleans, Louisiana, USA

    Adam I. Riker

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Peace, K.M., Herbert, G.S., Vreeland, T.J., Clifton, G.T., Peoples, G.E. (2018). Therapeutic Cancer Vaccines for Melanoma. In: Riker, A. (eds) Melanoma. Springer, Cham. https://doi.org/10.1007/978-3-319-78310-9_33

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-78310-9_33

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-78309-3

  • Online ISBN: 978-3-319-78310-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation