Chances are that active immunotherapy could operate more efficiently early during tumour progression or could prevent the disease in patients at a high risk of having malignant lesions

Chances are that active immunotherapy could operate more efficiently early during tumour progression or could prevent the disease in patients at a high risk of having malignant lesions. 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 IFN when were co-cultured with IFN-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 malignancy vaccines, Melanoma, GM3 ganglioside, CD8 T cells Introduction Most therapeutic cancer vaccines trials have been performed in advanced and heavily treated cancer patients. In this stage of the disease, the vaccination is usually poorly effective due to that, the immune system is not able to overcome tumour-induced or therapy-induced immunosuppression [1]. Many of the problems that WS 12 diminish therapeutic effects of cancer vaccines would not need to be considered in the setting of tumour prevention. An immune system that is primed against tumour antigens would be expected WS 12 to eliminate the tumour before it can suppress and evade the immune response. Consequently, preventive immunotherapy is an attractive strategy for patients at a high risk of having cancer, including viral-associated malignancies such as hepatocellular carcinoma [2] and cervical cancer [3], with some studies still in progress. In the case of melanoma, epidemiologic studies have identified environmental, host and genetic risk factors in which are included sun exposure, multiple banal or dysplastic nevi, fair skin, familial melanoma and susceptibility genes [4]. The chances of success of vaccines for cancer prevention depend on the selection of target antigens that are essential for tumour growth and progression. In this sense, GM3 ganglioside is usually a glycolipid present in WS 12 normal tissue but overexpressed on tumours like melanomas [5]. The immunosuppressive properties of this molecule and its important role in tumour progression make this self antigen a potential target for preventive immunotherapy of this neoplasm. For several years, gangliosides were considered as T cell impartial antigens because they were not presented to T lymphocytes by the major histocompatibility complex as regular peptide antigens [6]. However, this category became controversial due to the obtaining of CD1-restricted T cells specific for gangliosides in healthy donors and multiple sclerosis patients [7]. Several studies have shown that tumour-associated gangliosides are immunogenic in melanoma patients and that antibodies against them have a favorable prognostic effect [8]. The role of antibodies in the antitumour Rabbit Polyclonal to HDAC3 effect of ganglioside vaccines has been considered to be predominant, if not unique [9, 10]. However, the involvement of T cells in the antitumour protection induced by ganglioside-based vaccines has not yet been described. This is an important issue, since if a strong cellular immune response could be elicited, then immunological memory could be long lasting, eradicating tumour before it becomes clinically obvious. The GM3-based vaccine is composed by very small size proteoliposomes (VSSP) resulting from the hydrophobic conjugation of GM3 ganglioside with membrane proteins (VSSP/GM3) [11]. We have previously shown that preventive immunization of C57BL/6 mice with this nanoparticulated immunogen consistently elicited the rejection of B16 melanoma cells [12, 13]. However, the precise mechanisms by which this vaccine confers tumour protection were unknown. In the present work, we examined the effect of in vivo depletion of lymphocyte populations on tumour protection induced by VSSP/GM3 vaccine in B16 melanoma model. We have also tested the role of anti-GM3 antibodies in the vaccine capacity to reject the tumour. We found that the induction of anti-GM3 IgG antibodies correlated with tumour protection. However, the depletion of CD4+ T cells during immunization phase did not affect the antitumour.