Advertisement

European Journal of Dermatology

, Volume 26, Issue 2, pp 138–143 | Cite as

Xenogeneic cell-based vaccine therapy for stage III melanoma: safety, immune-mediated responses and survival benefits

  • Galina V. Seledtsova
  • Alexey A. Shishkov
  • Erika A. Kaschenko
  • Andrey G. Goncharov
  • Natalya D. Gazatova
  • Victor I. Seledtsov
Therapy
  • 26 Downloads

Abstract

Background

New therapies for melanoma have yielded promising results, but their application is limited because of serious side-effects and only moderate impact on patient survival. Vaccine therapies may offer some hope by targeting tumor-specific responses, considering the immunogenic nature of melanomas.

Objectives

To investigate the safety profile and efficiency of a xenogeneic cell-based vaccine therapy in stage III melanoma patients and evaluate the survival rate in treated patients.

Materials and Methods

Twenty-seven stage III melanoma patients were immunized with a lyophilized xenogeneic polyantigenic vaccine (XPV) prepared from murine melanoma B16 and carcinoma LLC cells.

Results

Neither grade III/IV toxicities, nor clinically significant changes in blood and biochemical parameters were noted after an induction course of 10 XPV subcutaneous immunizations. No laboratory or clinical signs of systemic autoimmunity were documented. Following 10 vaccinations, a relative increase in the numbers of circulating memory CD4+CD45RO+ T cells (but not CD8+ CD45RO+ T cells)was observed. Peripheral blood mononuclear cells obtained from XPV-treated patients demonstrated increased proliferative responses to human BRO melanoma-associated antigens and marked increases in serum levels of IFN and IL-8. Serum levels of TNF-, IL-4 and IL-6 were not affected. The overall five-year survival rate in the treated patients was significantly higher than that in 27 control patients with matched clinical and prognostic characteristics (55% vs 18%).

Conclusion

XPV-based immunotherapy could be maximally effective when started as early as possible before or after surgical excision of the primary tumor and local metastases, i.e. when tumor-mediated suppressive effects on immunity are minimal.

Key words

stage III melanoma xenogeneic polyantigenic vaccine toxicity safety memory T cell survival rate 

Abbreviations

Ab

antibody

IFN

interferon

IL

interleukin

M

mean

PBMC

peripheral blood mononuclear cell

SEM

standard error of the mean

SI

stimulation index

TAA

tumor-associated antigen

TNF

tumor necrosis factor

XPV

xenogeneic polyantigenic vaccine

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Weiss SA, Chandra S, Pavlick AC. Update on vaccines for high-risk melanoma. Curr Treat Options Oncol 2014; 15: 269–80.CrossRefPubMedGoogle Scholar
  2. 2.
    Shah DJ, Dronca RS. Latest advances in chemotherapeutic, targeted, and immune approaches in the treatment of metastatic melanoma. Mayo Clin Proc 2014; 89: 504–19.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Gyorki DE, Spillane J, Speakman D, Shackleton M, Henderson MA. Current management of advanced melanoma: a transformed landscape. ANZ J Surg 2014; 84: 612–7.CrossRefPubMedGoogle Scholar
  4. 4.
    Seledtsov VI, Shishkov AA, Seledtsova GV. Xenovaccinotherapy for cancer. In: Ozdemir O, editor. Current cancer treatment-novel beyond conventional approaches. InTech, 2011, p. 415–28.Google Scholar
  5. 5.
    Strioga MM, Darinskas A, Pasukoniene V, Mlynska A, Ostapenko V, Schijns V. Xenogeneic therapeutic cancer vaccines as breakers of immune tolerance for clinical application: to use or not to use? Vaccine 2014; 32: 4015–24.CrossRefPubMedGoogle Scholar
  6. 6.
    Seledtsov VI, Shishkov AA, Surovtseva MA, et al. Xenovaccinotherapy for melanoma. Eur J Dermatol 2006; 16: 655–61.PubMedGoogle Scholar
  7. 7.
    Seledtsov VI, Niza NA, Surovtseva MA, et al. Xenovaccinotherapy for colorectal cancer. Biomed Pharmacother 2007; 61: 125–30.CrossRefPubMedGoogle Scholar
  8. 8.
    Lockshin A, Giovanella BC, de Ipolyi PD, et al. Exceptional lethality for nude mice of cells derived from a primary human melanoma. Cancer Res 1985; 45: 345–50.PubMedGoogle Scholar
  9. 9.
    Galili U. Interaction of the natural anti-gal antibody with agalactosyl epitopes: a major obstacle for xenotransplantation in humans. Immunol Today 1993; 14: 480–2.CrossRefPubMedGoogle Scholar
  10. 10.
    Becht E, Goc J, Germain C, et al. Shaping of an effective immune microenvironment to and by cancer cells. Cancer Immunol Immunother 2014; 63: 991–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Seledtsov VI, Goncharov AG, Seledtsova GV. Clinically feasible approaches to potentiating cancer cell-based immunotherapies. Hum Vaccin Immunother 2015; 11(4): 851–69.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Spranger S, Gajewski T. Rational combinations of immunotherapeutics that target discrete pathways. J Immunother Cancer 2013; 1: 16.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Seledtsov VI, Seledtsova GV. A balance between tissue-destructive and tissue-protective immunities: a role of toll-like receptors in regulation of adaptive immunity. Immunobiology 2012; 217: 430–5.CrossRefPubMedGoogle Scholar

Copyright information

© John Libbey Eurotext 2016

Authors and Affiliations

  • Galina V. Seledtsova
    • 1
  • Alexey A. Shishkov
    • 1
  • Erika A. Kaschenko
    • 1
  • Andrey G. Goncharov
    • 2
  • Natalya D. Gazatova
    • 2
  • Victor I. Seledtsov
    • 2
  1. 1.Institute of Fundamental and Clinical ImmunologyNovosibirskRussia
  2. 2.lmmanuel Kant Baltic Federal UniversityKaliningradRussia

Personalised recommendations