Dendritic cells (II): Role and therapeutic implications in cancer

Abstract

The potential to harness the effectiveness and specificity of the immune system underlies the growing interest in cancer immunotherapy. One such approach uses bone marrow-derived dendritic cells (DCs), phenotypically distinct and very potent antigen-presenting cells, to present tumour-associated antigens (TAAgs) and, thereby, generate tumour-specific immunity. Support for this strategy comes from animal studies that have demonstrated that DCs, when loaded ex vivo with tumour Ags or pulsed with peptides and administered to cancer-bearing hosts, can elicit T cell-mediated cancer destruction. These observations have led to clinical trials designed to investigate the immunological and clinical effects of Ag-pulsed DCs administered as a therapeutic vaccine to patients with cancer. In the design and conduct of such trials, important considerations include Ag selection, methods for introducing TAAgs into MHC class I and II processing pathways, methods for isolating and activating DCs, and route of administration. Although current DC-based vaccination methods are cumbersome and complex, promising preliminary results from clinical trials in patients with malignant lymphoma, melanoma, and prostate cancer suggest that immuno-therapeutic strategies, that take advantage of the unique properties of DCs, may ultimately prove both efficacious and widely applicable treatment in patients with cancer.