Dendritic cell-based vaccines: barriers and opportunities

Abstract

Dendritic cells (DCs) have several characteristics that make them an ideal vehicle for tumor vaccines, and with the first US FDA-approved DC-based vaccine in use for the treatment of prostate cancer, this technology has become a promising new therapeutic option. However, DC-based vaccines face several barriers that have limited their effectiveness in clinical trials. A major barrier includes the activation state of the DC. Both DC lineage and maturation signals must be selected to optimize the antitumor response and overcome immunosuppressive effects of the tumor microenvironment. Another barrier to successful vaccination is the selection of target antigens that will activate both CD8(+) and CD4(+) T cells in a potent, immune-specific manner. Finally, tumor progression and immune dysfunction limit vaccine efficacy in advanced stages, which may make DC-based vaccines more efficacious in treating early-stage disease. This review underscores the scientific basis and advances in the development of DC-based vaccines, focuses on current barriers to success and highlights new research opportunities to address these obstacles.

Figure 1. Dendritic cell phenotype and subsequent T-cell polarization

Various factors affect the mature DC phenotype that in turn lead to the production of different cytokines, which then polarize T cells, alter the cytokine milieu and affect the ultimate nature of the immune response. DCs of different phenotypes secrete cytokines that exert their effect on naive T cells to polarize them towards phenotypes including Th1, Th2, Th17 and the immunosuppressive Treg cells. These T cells in turn are characterized by their own corresponding cytokine secretion profile; black arrows indicate activating factors; blue arrows indicate inhibition. DC: Dendritic cell; TLR: Toll-like receptor.