Dendritic cell-based therapeutic cancer vaccines: past, present and future.

Abstract

Dendritic cells (DCs) are professional antigen presenting cells, which play a pivotal role in antigen-specific (Ag-specific) T cell immunity. Malignancies have the capacity to inactivate DCs and effector T cells or to evade circulating antitumor immunity by expressing immune inhibitory molecules and/or secreting immunosuppressive cytokines. For this reason, ex-vivo-generated DCs [1] or in-vivo-DC-targeting [2] has been studied intensively over the past decade or development as a potential therapeutic cancer vaccine. Understanding how DCs induce, regulate, and maintain T cell immunity is essential for the design of novel cancer vaccines with improved clinical efficacy. Once activated, antigen-pulsed DCs are geared toward the launching of Ag-specific immunity, leading to T cell proliferation and differentiation into effector T cells. DCs are also important in triggering humoral immunity partly due to their capacity to directly interact with B cells and to present unprocessed antigens. There are examples of DC-based tumor vaccines being used successfully in clinical practice. Sipuleucel-T, the first Food and Drug Administration (FDA)-approved DC vaccine (Dendreon Corp.) has been found to be somewhat effective in the treatment of human prostate cancer [3]. As of 2014, 289 clinical studies of DC-based cancer vaccines are registered and under investigation (2014, http://www.clinicaltrials.gov). Among the 289 cases, 2 are in phase IV, 6 in phase III, 3 in phase II & III, 74 in phase II, 76 in phase I & II, 109 in phase I, and 3 in phase 0, underscoring the potential clinical significance of this therapy. In this editorial, we will discuss the evolution of DC-based cancer vaccine strategy, and future implications, with an emphasis on the efficacy and limitations of DC-based vaccine. Better understanding of DC biology and manipulation of activated DCs will allow DC scientists to produce the next generation of highly efficient cancer vaccines for cancer patients.