Human dendritic cells: natural adjuvants in antitumor immunotherapy

Although T-cell-defined tumor antigens have recently been identified in sev eral tumors, human neoplastic cells are considered to be poorly immunogenic . The development of clinical approaches to the immunotherapy of human tumo rs thus requires the identification of effective adjuvants. Dendritic cells (DC) are a specialized system of antigen-presenting cells (APC) that could be utilized as natural adjuvants to elicit antitumor immune responses. In an attempt to overcome the problem of the low frequency of mature DC in per ipheral blood, several methods have been applied for the ex vivo generation of human DC by culturing mobilized CD34(+) cells or monocytes with combina tions of cytokines. As shown in murine models as well as in the human syste m, after loading with peptides or tumor lysates or infection with recombina nt viral vectors, DC expressing tumor antigens are able to elicit specific antitumor T cells and to mediate tumor regression. These initial results su ggest that this new approach may lead to effective antitumor responses even in heavily pretreated patients bearing advanced cancers, but further clini cal trials are required to validate the efficacy of vaccination with tumor- antigen loaded DC.