Treatment of Prostate Cancer
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.
Therapeutic options for patients with progressive disease under androgen deprivation therapy comprise secondary hormonal manipulation and nonhormonal therapy such as chemotherapy. In the management of metastatic hormone-refractory PCa (HRPC), chemotherapy with docetaxel serves as reference treatment due to the demonstrated significant survival benefit. In patients with HRPC, bisphosphonates are useful for the treatment of skeletal complications and pain relief thereby improving quality of life and also providing a suitable medication for palliative care.
Despite of the therapeutic benefit of these approaches and the achieved prolongation of overall survival, additional treatment strategies are needed to prevent progression from localized to advanced disease and to further improve survival outcomes for patients with advanced PCa.
DCs play a crucial role for the induction of innate and adaptive antitumor immune responses. Thus, they efficiently activate and expand tumor-reactive CD8+ CTLs and CD4+ T cells. In addition, DCs can markedly improve the immunomodulatory and cytotoxic potential of natural killer cells and can directly mediate tumor-directed cytotoxicity. Due to their various antitumor effects, DCs emerged as promising candidates for the treatment of PCa patients. Consequently, several clinical trials enrolling PCa patients were conducted, which were based on the administration of DCs pulsed with TAA-derived peptides, protein, or RNA. studies demonstrated that DC-based immunotherapeutic strategies represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. Recently, sipuleucel-T consisting of PA2024 fusion protein-loaded APCs was approved by the United States Food and Drug Administration for the treatment of asymptomatic or minimally symptomatic, metastatic HRPC.