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 IFNgamma when were co-cultured with IFNalpha-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.