Efficacy of Dendritic Cells Matured Early with OK-432 (Picibanil®), Prostaglandin E₂, and Interferon-α as a Vaccine for a Hormone Refractory Prostate Cancer Cell Line

Abstract

Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil®) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-α. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-α (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-α (T), TNF-α and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods.

Interferon-α in the generation of monocyte-derived dendritic cells: recent advances and implications for dermatology

“…One study showed that the antitumour effects of a DC–prostate cancer cell line fusion vaccine treated with Streptococcus ‐derived immunotherapeutic agent, prostaglandin E 2 and IFN‐α is superior to that of the hybrids using conventional maturation methods 50 . Another group showed that CD40 ligand may represent the stimulus to be preferably used for inducing the full maturation of IFN‐DCs 4 .…”

Cell‑cell fusion as an important mechanism of tumor metastasis (Review)

“…Although cell fusion between BMDCs and somatic cells may be the origin of TSCs, the hybrid cells that form as a result of the fusion of human HSCs and esophageal carcinoma cells did not generate esophageal TSCs (52,53). DC-cancer cell fusion vaccines are an attractive modality for the treatment of several types of cancers, such as prostate, liver, gastric, colorectal, lung and breast cancer (54)(55)(56)(57)(58)(59)(60)(61)(62)(63). The cytotoxic T chemokine interferon-induced protein-10 was demonstrated to enhance the antitumor effects of DC/tumor cell fusion vaccines by alleviating the immunosuppressive tumor environment (64).…”

“…Glycoprotein B (gB) of VZV was reported to serve a role in cell-cell fusion (94). Strict regulation of VZV gB/gH-gL-mediated cell-cell fusion between Mel-DSP2 cells and CHO-DSP1 cells through gBcyt and gHcyt was revealed to be required for effective viral propagation (55). The identification of the role of the gB lysine cluster in cell-cell fusion regulation revealed the molecular mechanisms that govern VZV syncytium formation during infection (55).…”

Effects of programmed death-ligand 1 expression on OK-432 immunotherapy following transurethral resection in non-muscle invasive bladder cancer

“…OK-432 (also termed Picibanil), which is a penicillin-killed and lyophilized preparation of a low-virulence strain of Streptococcus pyogenes (group A), has been successfully used as an immunotherapeutic agent against numerous types of malignancies ( 7 – 10 ). It has been reported that OK-432 elicits antitumor effects by stimulating immunocompetent cells, including macrophages, T cells and natural killer (NK) cells, and by inducing helper T-cell 1-type cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, IL-8, IL-10, IL-12 and IL-18 ( 11 , 12 ), which may augment cytotoxic T lymphocytes to antitumor cells.…”