New perspectives in dendritic cell-based cancer immunotherapy

Dendritic cells are professional antigen-presenting cells with the unique c apacity to initiate primary immune responses. Recently, several procedures to Generate large numbers of dendritic cells from circulating precursors, i ncluding peripheral blood monocytes and CD34+ stem cells, have been develop ed. Stimulation with antigen-loaded dendritic cells was shown to break tole rance to tumour-associated antigens and to induce antitumour cytotoxic immu ne responses in vivo. Hence, numerous attempts to optimise delivery of tumo ur antigens to dendritic cells, as well as routes and schedules of administ ration to cancer patients, are currently under way. The first dendritic cel l clinical studies have indicated this form of vaccination as feasible and safe; furthermore, in some cases, objective clinical responses were observe d, even in patients heavily pretreated with standard chemo/radiotherapy app roaches. These preliminary data, although encouraging, require further exte nsive investigations, which should address the technical and biological pro blems of manipulating human dendritic. cells, as well as the clinical setti ngs which could benefit from an immunotherapeutic approach. Dendritic cells (DCs) are recognised as the most powerful antigen-presentin g cells (APCs) with the unique ability to stimulate naive resting T cells a nd to initiate primary immune responses in vitro and in vivo.([1-3]) Severa l attempts have recently been performed to verify the feasibility and effic acy 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 th e discovery of culture conditions enabling the generation of sufficient num bers of DCs in vitro from both CD34+ precursors([4-8]) and adherent blood m onocytes,([9-12]) thus making them a suitable candidate for vaccination pro tocols. This review aims to present an overview of the first published and ongoing DC-based vaccination studies.