New perspectives in dendritic cell-based cancer immunotherapy

Dendritic cells are professional antigen-presenting cells with the unique capacity to initiate primary immune responses. Recently, several procedures to Generate large numbers of dendritic cells from circulating precursors, including peripheral blood monocytes and CD34+ stem cells, have been developed. Stimulation with antigen-loaded dendritic cells was shown to break tolerance to tumour-associated antigens and to induce antitumour cytotoxic immune responses in vivo. Hence, numerous attempts to optimise delivery of tumour antigens to dendritic cells, as well as routes and schedules of administration to cancer patients, are currently under way. The first dendritic cell clinical studies have indicated this form of vaccination as feasible and safe; furthermore, in some cases, objective clinical responses were observed, even in patients heavily pretreated with standard chemo/radiotherapy approaches. These preliminary data, although encouraging, require further extensive investigations, which should address the technical and biological problems of manipulating human dendritic. cells, as well as the clinical settings which could benefit from an immunotherapeutic approach. Dendritic cells (DCs) are recognised as the most powerful antigen-presenting cells (APCs) with the unique ability to stimulate naive resting T cells and to initiate primary immune responses in vitro and in vivo.([1-3]) Several attempts have recently been performed to verify the feasibility and efficacy of inducing targeted antitumour immune responses in vivo in the context of phase I/II clinical trials. The use of DC-based approaches relies on the discovery of culture conditions enabling the generation of sufficient numbers of DCs in vitro from both CD34+ precursors([4-8]) and adherent blood monocytes,([9-12]) thus making them a suitable candidate for vaccination protocols. This review aims to present an overview of the first published and ongoing DC-based vaccination studies.