Dendritic cell-based vaccine for pancreatic cancer in Japan

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 DC-maturating 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 small-scale 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 progression-free survival as compared to the DTH negative patients. The activation of antigen-specific immune responses by DC vaccine in combination with standard chemotherapy 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.

Keywords: Anti-cancer immunity; Cancer immunotherapy; Cancer vaccine; Dendritic cell; Pancreatic cancer.

Figure 1

The dendritic cells play central roles in deciding the direction of host immune reactions as well as antigen presentation. A: Role of various dendritic cells in CD4⁺ T-cell differentiation; B: Antigen presentation and CTL induction under Th1 condition. CTL: Cytotoxic T lymphocytes; DC: Dendritic cell.

Figure 2

A Th1-inducing type of dendritic cell vaccine, Vaccell is made as follows. A: Preparation of the DC vaccine “Vaccell”; B and C: Vaccell for pancreatic cancer patients; B: Two hundred fifty five patients who received standard chemotherapy combined with DC vaccines were analyzed. DTH skin reaction after vaccination was an independent prognostic factor for better survival; B: The WT1-specific DTH positive patients showed significantly improved OS and PFS compared with the DTH negative patients[20,21]. DC: Dendritic cell; DTH: Delayed type hypersensitivity; PFS: Progressive-free survival; OS: Overall survival.