Dendritic cell-based immunotherapy for prostate cancer

Abstract

Dendritic cells (DCs) are professional antigen-presenting cells (APCs), which display an extraordinary capacity to induce, sustain, and regulate T-cell responses providing the opportunity of DC-based cancer vaccination strategies. Thus, clinical trials enrolling prostate cancer patients were conducted, which were based on the administration of DCs loaded with tumor-associated antigens. These clinical trials revealed that DC-based immunotherapeutic strategies represent safe and feasible concepts for the induction of immunological and clinical responses in prostate cancer patients. In this context, the administration of the vaccine sipuleucel-T consisting of autologous peripheral blood mononuclear cells including APCs, which were pre-exposed in vitro to the fusion protein PA2024, resulted in a prolonged overall survival among patients with metastatic castration-resistant prostate cancer. In April 2010, sipuleucel-T was approved by the United States Food and Drug Administration for prostate cancer therapy.

Figure 1

DC-based immunotherapeutic strategies for prostate cancer. DCs display a unique capacity to induce and maintain T-cell responses and emerged as promising candidates for vaccination strategies in prostate cancer therapy. Thus, DCs are loaded with PCa-associated antigen-derived peptides, protein, or RNA. Due to their high surface expression of HLA-peptide-complexes and costimulatory molecules, DCs efficiently activate and expand CD8⁺ CTLs and CD4⁺ T cells. CD8⁺ CTLs possess a profound capability to recognize and destroy tumor cells. CD4⁺ T cells enhance the capacity of DCs to induce CTLs by the interaction between CD40 on DCs and CD40 ligand on activated CD4⁺ T cells. In addition, they provide help for the maintenance and expansion of CTLs by secreting cytokines and are able to eradicate tumor cells directly. CTLs: cytotoxic T cells; DCs: dendritic cells; HLA: human leukocyte antigen; IL: interleukin; IFN: interferon; TCR: T cell receptor; TU: tumor cells.