Cancer Immunology, Immunotherapy

, Volume 57, Issue 12, pp 1771–1780

Immunization with a GM3 ganglioside nanoparticulated vaccine confers an effector CD8+ T cells-mediated protection against melanoma B16 challenge

Authors

    • Department of VaccinesCenter of Molecular Immunology
  • Circe Mesa
    • Department of VaccinesCenter of Molecular Immunology
  • Audry Fernández
    • Department of VaccinesCenter of Molecular Immunology
  • Luis E. Fernández
    • Department of VaccinesCenter of Molecular Immunology
Original Article

DOI: 10.1007/s00262-008-0503-8

Cite this article as:
Mazorra, Z., Mesa, C., Fernández, A. et al. Cancer Immunol Immunother (2008) 57: 1771. doi:10.1007/s00262-008-0503-8

Abstract

Preventive immunotherapy is an attractive strategy for patients at a high risk of having cancer. The success of prophylactic cancer vaccines would depend on the selection of target antigens that are essential for tumour growth and progression. The overexpression of GM3 ganglioside in murine and human melanomas and its important role in tumour progression makes this self antigen a potential target for preventive immunotherapy of this neoplasm. We have previously shown that preventive administration of a GM3-based vaccine to C57BL/6 mice elicited the rejection of the GM3 positive-B16 melanoma cells in most of the animals. Despite the crucial role of cellular immune response in tumour protection, the involvement of T cells in anti-tumour immunity of ganglioside vaccines is not described. Here, we examined the mechanisms by which this immunogen confers tumour protection. We have found that induction of anti-GM3 IgG antibodies correlated with tumour protection. Surprisingly, CD8+ T cells, but not NK1.1+ cells, are required in the effector phase of the antitumour immune response. The depletion of CD4+ T cells during immunization phase did not affect the anti-tumour activity. In addition, T cells from surviving-immunized animals secreted IFNγ when were co-cultured with IFNα-treated B16 melanoma cells or DCs pulsed with melanoma extract. Paradoxically, in spite of the glycolipidic nature of this antigen, these findings demonstrate the direct involvement of the cellular immune response in the anti-tumour protection induced by a ganglioside-based vaccine.

Keywords

Preventive cancer vaccines Melanoma GM3 ganglioside CD8 T cells

Abbreviations

VSSP

Very small size proteoliposomes

FCS

Fetal calf serum

OMP

Outer membrane proteins

MAbs

Monoclonal antibodies

PI

Propidium iodide

PNPP

p-Nitrophenylphosphate

CMC

Complement-mediated cytotoxicity

bmDCs

Bone-marrow-derived dendritic cells

Copyright information

© Springer-Verlag 2008