A phase I trial in melanoma patients using dendritic cells pulsed with a novel synthetic iNKT cell agonist

点击翻译按钮获取中文摘要

Tumour immunology is now on a very solid and conceptual footing. The challenge remains to translate these results into the clinic. There is a great expectation that cancer vaccines will offer advantages over conventional cancer treatments . Vaccines are likely to produce fewer and milder side-effects than chemotherapy and radiotherapy as they specifically target cancer cells only. The ideal immune response to a cancer vaccine would be ?integrated , meaning that all components of the immune system, killer cells, helper cells and antibodies, are generated to target tumour cells, leading to the destruction of the cancer cells. Such integrated immune responses require that vaccination strategies facilitate an optimal cross-talk between different cells of the immune system. Current vaccination strategies, based on the use of recombinant attenuated viruses, are failing to trigger such an integrated response, since immune responses in patients vaccinated with current vaccination protocols are orders of magnitudes weaker than those immune responses observed during natural infections. Optimizing vaccination protocols requires a deeper understanding of the signals that the immune system coordinates to respond to pathogenic infection. Compounds that mimic these signals may therefore be exploited as adjuvants in current vaccination strategies. Advances in molecular technology have permitted the design of ?subunit? vaccines directed at protein targets, providing immunotherapy with a degree of specificity that was not possible using traditional vaccines based on live attenuated viruses.Over the last few years we have characterised a series of synthetic compounds capable of activating a population of cells, called invariant NKT cells, which orchestrate the maturation of professional antigen presenting cells (dendritic cells) resulting in the activation of killer cells, helper cells and antibody producing cells. The results of these studies have been possible through a concerted effort between immunologists, structural biologists and organic chemists. We are now very keen to translate these results into the clinic to assess whether the results obtained in pre-clinical models can be applied to cancer patients and trigger an integrated cancer specific immune response.