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

Abstract

Editorial 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 cyto-kines. 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 immu-nity 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 di-rectly 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 un-der 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 vac-cine. 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. First Generation DC Vaccines For the first generation of DC vaccines, patient-isolated or ex-vivo-generated mono-cyte-derived DCs (MoDCs) were used without additional modifications. Those pri-mary DC vaccines were loaded with tumor lysates, recombinant tumor antigens or synthetic peptides. The early clinical trials of DC vaccines established the safety and feasibility of DC-based cancer vaccines, with relatively lower toxicity when compared with chemotherapy or radiation therapy. However, these unmodified MoDC vaccines only led to a tumor regression rate of 3.3% in patients with cancer. Because of this, pep-tide-loaded DCs were utilized, and demonstrated an improved tumor regression rate