Skip to main content
SpringerLink
Log in

Tumour Cell-Based Vaccines for the Treatment of Melanoma

  • Leading Article
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

Melanoma is generally resistant to chemotherapy and radiation therapy. Its unique immunological properties lend support to developing innovative new therapies via manipulation of the patient’s own immune system. The use of whole-cell—based tumour vaccines, including autologous, whole-cell allogeneic and cytokine gene-modified vaccines, as well as tumour lysate vaccines, for active specific immunotherapy of melanoma, is discussed in detail with regard to rationale and available clinical data. Although phase II data on the use of melanoma vaccine in the adjuvant setting show promise, there is no randomised phase III trial demonstrating the efficacy of active specific immunotherapy for melanoma. The coming years will bring the results of several pivotal multicentre phase III trials testing the clinical utility of active specific immunotherapy in the management of melanoma.

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

Similar content being viewed by others

Notes

  1. Use of tradenames is for identification purposes only, and does not imply endorsement.

References

  1. Barth A, Wanek LA, Morton DL. Prognostic factors in 1,521 melanoma patients with distant metastases. J Am Coll Surg 1995; 181: 193–201

    PubMed  CAS  Google Scholar 

  2. McClay EF, McClay ME. Systemic chemotherapy for the treatment of metastatic melanoma. Semin Oncol 1996; 23: 744–53

    CAS  Google Scholar 

  3. Chapman PB, Einhorn LH, Meyers ML, et al. Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol 1999; 17: 2745–51

    PubMed  CAS  Google Scholar 

  4. Morton DL, Malmgren RA, Holmes EC, et al. Demonstration of antibodies against human malignant melanoma by immunofluorescence. Surgery 1968; 64: 233–40

    PubMed  CAS  Google Scholar 

  5. Lewis MG, Ikonopisov RL, Nairn RC, et al. Tumour-specific antibodies in human malignant melanoma and their relationship to the extent of the disease. BMJ 1969; 3: 547–52

    Article  PubMed  CAS  Google Scholar 

  6. Canevari S, Fossati G, Della Porta G, et al. Humoral cytotoxicity in melanoma patients and its correlation with the extent and course of the disease. Int J Cancer 1975; 16: 722–9

    Article  PubMed  CAS  Google Scholar 

  7. Bodurtha AJ, Chee DO, Laucius JF, et al. Clinical and immunological significance of human melanoma cytotoxic antibody. Cancer Res 1975; 35: 189–93

    PubMed  CAS  Google Scholar 

  8. Hellstrom I, Hellstrom KE, Sjogren HO, et al. Demonstration of cell-mediated immunity to human neoplasms of various histological types. Int J Cancer 1971; 7: 1–16

    Article  PubMed  CAS  Google Scholar 

  9. Topalian SL, Solomon D, Rosenberg SA. Tumor-specific cytolysis by lymphocytes infiltrating human melanomas. J Immunol 1989; 142: 3714–25

    PubMed  CAS  Google Scholar 

  10. Chen Q, Hersey P. MHC-restricted responses of CD8+ and CD4+ T-cell clones from regional lymph nodes of melanoma patients. Int J Cancer 1992; 51: 218–24

    Article  PubMed  CAS  Google Scholar 

  11. Mackensen A, Carcelain G, Viel S, et al. Direct evidence to support the immunosurveillance concept in a human regressive melanoma. J Clin Invest 1994; 93: 1397–402

    Article  PubMed  CAS  Google Scholar 

  12. Rosenberg SA, Lotze MT, Muul LM, et al. Aprogress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 1987; 316: 889–997

    Article  PubMed  CAS  Google Scholar 

  13. Sun Y, Paschen A, Schadendorf D. Cell-based vaccination against melanoma: background, preliminary results, and perspective. J Mol Med 1999; 77(8): 593–608

    Article  PubMed  CAS  Google Scholar 

  14. Rosenberg S A. A new era for cancer immunotherapy based on the genes that encode cancer antigens. Immunity 1999; 10(3): 281–7

    Article  PubMed  CAS  Google Scholar 

  15. Renkvist N, Castelli C, Robbins PF, et al. A listing of human tumor antigens recognized by T cells. Cancer Immunol Immunother 2001; 50: 3–15

    Article  PubMed  CAS  Google Scholar 

  16. Berd D, Herlyn M, Koprowski H, et al. Flow cytometric determination of the frequency and heterogeneity of expression of human melanoma-associated antigens. Cancer Res 1989; 49: 6840–4

    PubMed  CAS  Google Scholar 

  17. Degiovanni G, Lahaye T, Herin M, et al. Antigenic heterogeneity of a human melanoma tumor detected by autologous CTL clones. Eur J Immunol 1988; 18: 671–6

    Article  PubMed  CAS  Google Scholar 

  18. Berd D, Maguire Jr HC, McCue P, et al. Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients. J Clin Oncol 1990; 8(11): 1858–67

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  20. Sensi M, Farina C, Maccalli C, et al. Clonal expansion of T lymphocytes in human melanoma metastases after treatment with a hapten-modified autologous tumor vaccine. J Clin Invest 1997; 99(4): 710–7

    Article  PubMed  CAS  Google Scholar 

  21. Baars A, Claessen AM, van den Eertwegh AJ, et al. Skin tests predict survival after autologous tumor cell vaccination in metastatic melanoma: experience in 81 patients. Ann Oncol 2000; 11: 965–70

    Article  PubMed  CAS  Google Scholar 

  22. Dillman RO, Nayak SK, Barth NM, et al. Clinical experience with autologous tumor cell lines for patient-specific vaccine therapy in metastatic melanoma. Cancer Biother Radiopharm 1998; 13: 165–76

    Article  PubMed  CAS  Google Scholar 

  23. Leong SP, Enders-Zohr P, Zhou YM, et al. Recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) and autologous melanoma vaccine mediate tumor regression in patients with metastatic melanoma. J Immunother 1999; 22: 166–74

    Article  PubMed  CAS  Google Scholar 

  24. Thomas MC, Greten TF, Pardoll DM, et al. Enhanced tumor protection by granulocyte-macrophage colony-stimulating factor expression at the site of an allogeneic vaccine. Hum Gene Ther 1998; 9: 835–43

    Article  PubMed  CAS  Google Scholar 

  25. Crowley NJ, Darrow TL, Quinn-Allen MA, et al. MHC-restricted recognition of autologous melanoma by tumor-specific cytotoxic T cells: evidence for restriction by a dominant HLA-A allele. J Immunol 1991; 146: 1692–9

    PubMed  CAS  Google Scholar 

  26. Valmori D, Lienard D, Waanders G, et al. Analysis of MAGE-3-specific cytolytic T lymphocytes in human leukocyte antigen-A2 melanoma patients. Cancer Res 1997; 57: 735–41

    PubMed  CAS  Google Scholar 

  27. Hayashi Y, Hoon DS, Park MS, et al. Cytotoxic T cell lines recognize autologous and allogeneic melanomas with shared or cross-reactive HLA-A. Cancer Immunol Immunother 1992; 34: 419–23

    Article  PubMed  CAS  Google Scholar 

  28. Morton DL, Foshag LJ, Hoon DSB, et al. Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine. Ann Surg 1992; 216: 463–82

    Article  PubMed  CAS  Google Scholar 

  29. Chan AD, Morton DL. Active immunotherapy with allogeneic tumor cell vaccines: present status. Semin Oncol 1998; 25: 611–22

    PubMed  CAS  Google Scholar 

  30. Hsueh EC, Nathanson L, Foshag LJ, et al. Active specific immunotherapy with polyvalent melanoma cell vaccine in patients with in-transit melanoma metastases. Cancer 1999; 85: 2160–9

    Article  PubMed  CAS  Google Scholar 

  31. Morton DL, Barth A. Vaccine therapy for malignant melanoma. CA Cancer J Clin 1996; 46: 225–44

    Article  PubMed  CAS  Google Scholar 

  32. Hsueh EC, Nizze A, Essner R, et al. Adjuvant immunotherapy with polyvalent melanoma cell vaccine (PMCV) prolongs survival after complete resection of distant melanoma metastases: matched pair analysis [abstract]. Proc Am Soc Clin Oncol 1997; 16: 492a

    Google Scholar 

  33. Hsueh EC, Gupta RK, Qi K, et al. Correlation of specific immune responses with survival in melanoma patients with distant metastases receiving polyvalent melanoma cell vaccine. J Clin Oncol 1998; 16: 2913–20

    PubMed  CAS  Google Scholar 

  34. Cascinelli N, Rumke P, MacKie R, et al. The significance of conversion of skin reactivity to efficacy of bacillus Calmette-Guerin (BCG) vaccinations given immediately after radical surgery in stage II melanoma patients. Cancer Immunol Immunother 1989; 28: 282–6

    Article  PubMed  CAS  Google Scholar 

  35. Eilber FR, Morton DL, Holmes EC, et al. Adjuvant immunotherapy with BCG in treatment of regional-lymph-node metastases from malignant melanoma. N Engl J Med 1976; 294: 237–40

    Article  PubMed  CAS  Google Scholar 

  36. Moller P, Sun Y, Dorbic T, et al. Vaccination with IL-7 genemodified autologous melanoma cells can enhance the antimelanoma lytic activity in peripheral blood of patients with a good clinical performance status: a clinical phase I study. Br J Cancer 1998; 77: 1907–6

    Article  PubMed  CAS  Google Scholar 

  37. Sun Y, Jurgovsky K, Moller P, et al. Vaccination with IL-12 gene-modified autologous melanoma cells: preclinical results and a first clinical phase I study. Gene Ther 1998; 5: 481–90

    Article  PubMed  CAS  Google Scholar 

  38. Soiffer R, Lynch T, Mihm M, et al. Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. Proc Natl Acad Sci USA 1998; 95: 13141–6

    Article  PubMed  CAS  Google Scholar 

  39. Abdel-Wahab Z, Weltz C, Hester D, et al. APhase I clinical trial of immunotherapy with interferon-gamma gene-modified autologous melanoma cells: monitoring the humoral immune response. Cancer 1997; 80: 401–12

    Article  PubMed  CAS  Google Scholar 

  40. Wittig B, Marten A, Dorbic T, et al. Therapeutic vaccination against metastatic carcinoma by expression-modulated and immunomodified autologous tumor cells: a first clinical phase I/II trial. Hum Gene Ther 2001; 12: 267–78

    Article  PubMed  CAS  Google Scholar 

  41. Arienti F, Sule-Suso J, Belli F, et al. Limited antitumor T cell response in melanoma patients vaccinated with interleukin-2 gene-transduced allogeneic melanoma cells. Hum Gene Ther 1996; 7: 1955–63

    Article  PubMed  CAS  Google Scholar 

  42. Belli F, Arienti F, Sule-Suso J, et al. Active immunization of metastatic melanoma patients with interleukin-2-transduced allogeneic melanoma cells: evaluation of efficacy and tolerability. Cancer Immunol Immunother 1997; 44: 197–203

    Article  PubMed  CAS  Google Scholar 

  43. Osante S, Schiphorst PP, Weijl NI, et al. Vaccination of melanoma patients with an allogeneic, genetically modified interleukin 2-producing melanoma cell line. Hum Gene Ther 2000; 11: 739–50

    Article  Google Scholar 

  44. Arienti F, Belli F, Napolitano F, et al. Vaccination of melanoma patients with interleukin 4 gene-transduced allogeneic melanoma cells. Hum Gene Ther 1999; 10: 2907–16

    Article  PubMed  CAS  Google Scholar 

  45. Mitchell MS. Perspective on allogeneic melanoma lysates in active specific immunotherapy. Semin Oncol 1998; 25: 623–35

    PubMed  CAS  Google Scholar 

  46. Mitchell MS, Harel W, Kan-Mitchell J, et al. Active specific immunotherapy of melanoma with allogeneic cell lysates. Rationale, results, and possible mechanisms of action. Ann N Y Acad Sci 1993; 690: 153–66

    Article  PubMed  CAS  Google Scholar 

  47. Mitchell MS, Harel W, Kempf RA, et al. Active-specific immunotherapy for melanoma. J Clin Oncol 1990; 8: 856–69

    PubMed  CAS  Google Scholar 

  48. Mitchell MS, Harel W, Groshen S. Association of HLA phenotype with response to active specific immunotherapy of melanoma. J Clin Oncol 1992; 10: 1158–64

    PubMed  CAS  Google Scholar 

  49. Elliott GT, McLeod RA, Perez J, et al. Interim results of a phase II multicenter clinical trial evaluating the activity of a therapeutic allogeneic melanoma vaccine (theraccine) in the treatment of disseminated malignant melanoma. Semin Surg Oncol 1993; 9: 264–72

    PubMed  CAS  Google Scholar 

  50. Wallack MK, McNally KR, Leftheriotis E, et al. A Southeastern Cancer Study Group phase I/II trial with vaccinia melanoma oncolysates. Cancer 1986; 57: 649–55

    Article  PubMed  CAS  Google Scholar 

  51. Wallack MK, Sivanandham M, Ditaranto K, et al. Increased survival of patients treated with a vaccinia melanoma oncolysate vaccine: second interim analysis of data from a phase III, multi-institutional trial. Ann Surg 1997; 226: 198–206

    Article  PubMed  CAS  Google Scholar 

  52. Wallack MK, Sivanandham M, Balch CM, et al. Surgical adjuvant active specific immunotherapy for patients with stage III melanoma: the final analysis of data from a phase III, randomized, double-blind, multicenter vaccinia melanoma oncolysate trial. J Am Coll Surg 1998; 187: 69–77

    Article  PubMed  CAS  Google Scholar 

  53. Huang AY, Golumbek P, Ahmadzadeh M, et al. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor Ag. Science 1994; 264: 961–5

    Article  PubMed  CAS  Google Scholar 

  54. Kurts C, Carbone FR, Barden M, et al. CD4+ T cell help impairs CD8+ T cell deletion induced by cross-presentation of self-antigens and favors autoimmunity. J Exp Med 1997; 186: 2057–62

    Article  PubMed  CAS  Google Scholar 

  55. Li Y, McGowan P, Hellstrom I, et al. Costimulation of tumor-reactive CD4+ and CD8+ T lymphocytes by B7, a natural ligand for CD28, can be used to treat established mouse melanoma. J Immunol 1994; 153: 421–8

    PubMed  CAS  Google Scholar 

  56. Cayeux S, Richter G, Noffz G, et al. Influence of gene-modified (IL-7, IL-4, and B7) tumor cell vaccines on tumor antigen presentation. J Immunol 1997; 158: 2834–2841

    PubMed  CAS  Google Scholar 

  57. Nestle FO, Alijagic S, Gilliet M, et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 1998; 4: 328–32

    Article  PubMed  CAS  Google Scholar 

  58. Mukherji B, Chakraborty NG, Yamasaki S, et al. Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells. Proc Natl Acad Sci USA 1995; 92: 8078–82

    Article  PubMed  CAS  Google Scholar 

  59. Chakraborty NG, Sporn JR, Tortora AF, et al. Immunization with a tumor-cell-lysate-loaded autologous-antigen-presenting-cell-based vaccine in melanoma. Cancer Immunol Immunother 1998; 47: 58–64

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Supported in part by grants CA87071 and CA12582 from the National Cancer Institute and by funding from the Wayne and Gladys Valley Foundation (Oakland).

Author information

Authors and Affiliations

  1. Sonya Valley Ghidossi Vaccine Laboratory of the Roy E. Coats Research Laboratories of the John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, California, 90404, USA

    Eddy C. Hsueh

Authors
  1. Eddy C. Hsueh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eddy C. Hsueh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hsueh, E.C. Tumour Cell-Based Vaccines for the Treatment of Melanoma. BioDrugs 15, 713–720 (2001). https://doi.org/10.2165/00063030-200115110-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00063030-200115110-00002

Keywords

Search

Navigation