Advances in dendritic cell-based vaccine of cancer
ABSTRACT
Dendritic cells (DCs) are potent antigen presenting cells that exist in virtually every tissue, and from which they capture antigens and migrate to secondary lymphoid organs where they activate naïve T cells. Although DCs are normally present in extremely small numbers in the circulation, recent advances in DC biology have allowed the development of methods to generate large numbers of these cells in vitro. Because of their immunoregulatory capacity, vaccination with tumor antigen-presenting DCs has been proposed as a treatment modality for cancer. In animal models, vaccination with DCs pulsed with tumor peptides, lysates, or RNA or loaded with apoptotic/necrotic tumor cells could induce significant antitumor CTL responses and antitumor immunity. However, the results from early clinical trails pointed to a need for additional improvement of DC-based vaccines before they could be considered as practical alternatives to the existing cancer treatment strategies. In this regard, subsequent studies have shown that DCs that express transgenes encoding tumor antigens are more potent primers of antitumor immunity both in vitro and in vivo than DCs simply pulsed with tumor peptides. Furthermore, DCs that have been engineered to express certain cytokines or chemokines can display a substantially improved maturation status, capacity to migrate to secondary lymphoid organs in vivo, and abilities to stimulate tumor-specific T cell responses and induce tumor immunity in vivo. In this review we also discuss a number of factors that are important considerations in designing DC vaccine strategies, including (i) the type and concentrations of tumor peptides used for pulsing DCs; (ii) the timing and intervals for DC vaccination/boostable data on DC vaccination portends bright prospects for this approach to tumor immune therapy, either alone or in conjunction with other therapies.