New perspectives in dendritic cell-based cancer immunotherapy.

ABSTRACT

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.