Dendritic cell-based vaccine for pancreatic cancer in Japan

Abstract

Abstract"Vaccell" is a dendritic cell (DC)-based cancer vaccine which has been established in Japan. The DCs play central roles in deciding the direction of host immune reactions as well as antigen presentation. We have demonstrated that DCs treated with a streptococcal immune adjuvant OK-432, produce interleukin-12, induce Th1-dominant state, and elicit anti-tumor effects, more powerful than those treated with the known DCmaturating factors. We therefore decided to mature DCs by the OK-432 for making an effective DC vaccine, Vaccell. The 255 patients with inoperable pancreatic cancer who received standard chemotherapy combined with DC vaccines, were analyzed retrospectively. Survival time of the patients with positive delayed type hypersensitivity (DTH) skin reaction was significantly prolonged as compared with that of the patients with negative DTH. The findings strongly suggest that there may be "Responders" for the DC vaccine in advanced pancreatic cancer patients. We next conducted a smallscale prospective clinical study. In this trial, we pulsed HLA class Ⅱ-restricted WT1 peptide (WT1-Ⅱ) in addition to HLA class Ⅰ-restricted peptide (WT1-Ⅰ) into the DCs. Survival of the patients received WT1-Ⅰ and -Ⅱ pulsed DC vaccine was significantly extended as compared to that of the patients received DCs pulsed with WT1-Ⅰ or WT1-Ⅱ alone. Furthermore, WT1-specific DTH positive patients showed significantly improved the overall survival as well as progressionfree survival as compared to the DTH negative patients. may be associated with a good clinical outcome in advanced pancreatic cancer. We are now planning a pivotal study of the Vaccell in appropriate protocols in Japan.

Current advances and outlooks in immunotherapy for pancreatic ductal adenocarcinoma

“…Briefly, there are three major vaccine platforms for PDAC: DCbased vaccines, tumour cell-based vaccines and bacterium-based vaccines. DCs are the most common platform, and DC-based vaccines have been tested in numerous clinical trials and thoroughly reviewed [139,140]. Another PDAC vaccine platform is the wholetumour cell vaccine platform using autologous and/or allogeneic cancer cells with or without genetic editing.…”

An overview of polyamine metabolism in pancreatic ductal adenocarcinoma

“…Dendritic cells play critical roles in directing host immune response and eliciting an antigen‐specific host defense . A recent report on a dendritic cell vaccine for pancreatic cancer suggested improved patient outcome . While the effect of spermine on dendritic cells in PDAC is unknown, a significant inverse correlation between spermine concentration and the percentage of dendritic cells expressing IL‐12 has been observed in breast cancers .…”

Phenotypic features of generated dendritic cells in patients with pancreatic cancer immunotherapy

“…Возможно лишь умеренное повышение температуры тела и слабость, что может быть связано с общим иммунным отве-том организма. Полученные результаты совпадают с данными M. Okamoto и соавт., которые проводили пилотные исследования эффективности ДК-вакци-нотерапии у больных РПЖ в Японии [15].…”