Immunotherapy with dendritic cells for prostate cancer

Abstract

Radical prostatectomy for prostate cancer is followed by PSA recurrence in up to 40% of patients. One third of patients with biochemical relapse progress to uncurable metastatic disease. Therefore, alternative treatment modalities are needed both in the situation of PSA recurrence and in hormone-refractory disease. Dendritic cells (DC) are the most powerful antigen-presenting cells, able to prime na€ ıve T-cells and to break peripheral tolerance and thus induce tumor immune responses. More than 400 prostate cancer patients have been treated with DC-based immunotherapy to date, and immune responses have been reported in two-thirds of these, resulting in clinical responses in almost half of the patients treated. Most responses, however, were modest and transient. Therefore, mechanisms of treatment failure and possibilities to improve vaccination efficacy are being discussed. ' 2007 Wiley-Liss, Inc.Key words: prostate cancer; immunotherapy; vaccination; dendritic cells Prostate cancer is the most frequently diagnosed malignancy and the second and third leading cause of cancer-related mortality among men in the United States and Europe, respectively.

Expression of CD137 on Hodgkin and Reed–Sternberg Cells Inhibits T-cell Activation by Eliminating CD137 Ligand Expression

“…Similarly, most tumor immunotherapy approaches aim at enhancing the anticancer immune response but have had little success in human patients (3,4). One common reason for the inability of immune cells to eliminate cancers and the inefficiency of tumor immunotherapy is that malignant cells are immunoedited and selected to avoid elimination by the immune system (5).…”

Combination use of immune complexes and a Ca2+ channel blocker azelnidipine enhances interleukin-12 p40 secretion without T helper type 17 cytokine secretion in human monocyte-derived dendritic cells

“…In conclusion, this study has indicated that FcR-mediated phagocytosis of ICs enhances IL-12 p40 monomer/ homodimer secretion from DC, and a Ca2 + channel blocker, azelnidipine, has an additive effect on this enhancement. Until the present, cancer immunotherapy using tumour peptide-or antigen-loading of immature DCs ex vivo has resulted in some clinical responses, but most of them were transient and insufficient [49][50][51]. The use of a Ca2…”

Immunotherapeutics in Development for Prostate Cancer

“…Finally, there is no validated gold standard for immune monitoring in immunotherapy studies [46]. Delayed-type hypersensitivity, enzyme-linked immunosorbent spot, and tetramer analysis/T-cell proliferation have all been used as measurements of the immune response.…”