WT1-pulsed Dendritic Cell Vaccine Combined with Chemotherapy for Resected Pancreatic Cancer in a Phase I Study

Abstract

Abstract. Background/Aim: Wilms' tumor 1 (WT1) is a tumor-associated antigen highly expressed in cancer. We examined the safety of WT1-peptide pulsed dendritic cell (WT1-DC) vaccine in combination withAlthough several treatment approaches, such as surgery and chemotherapy, have been used for treating pancreatic cancer, its prognosis remains poor, and further improvement in the treatment outcome is required (1-4). Recently, immunotherapy has been put forward as a new treatment approach for such cancer types with poor prognosis, and various methods have been examined in practice (1, 2, 5-7). In immunotherapy, selection of the tumor-associated antigen (TAA) is important. It has been reported that the Wilms' tumor 1 (WT1) antigen is highly expressed in various malignancies (8), including pancreatic cancer (8,9). Therefore, WT1 has been used as one of the targets of immunotherapy for pancreatic cancer (1, 7). For advanced pancreatic cancer, a WT1-peptide vaccine and WT1-peptide pulsed-dendritic cell (WT1-DC) vaccine have already been used in combination with chemotherapy agents, such as gemcitabine and S-1, in multiple studies, and its safety has been verified (10-16). Additionally, its clinical effects have been reported (11)(12)(13). Positive findings, such as WT1-specific delayed-type hypersensitivity after administration of the WT1-DC vaccine, reduced neutrophil/lymphocyte ratio in peripheral blood before or after administration, increased expression of CD83/human leukocyte antigen (HLA)-DR on DCs after administration, and no increase in interleukin-6 levels in peripheral blood after administration, have been reported as prognostic factors (13,15,16 (11,12).For patients diagnosed with primary pancreatic cancer, resection is the most important treatment, and implementation of postoperative chemotherapy can improve prognosis. In a recent report, the administration of S-1 alone was shown to be superior to that of gemcitabine for pancreatic cancer after resection (25). However, recurrence after surgery remains a serious problem. Therefore, the use of immunotherapy in combination with standard chemotherapy in the early phase can be considered as a strategy for the prevention of the recurrence of pancreatic cancer. Thus, in this study, we examined the safety of WT1-DC vaccine and acquisition of WT1-specific CTLs after administration of the vaccine with OK-432 as an adjuvant combined with chemotherapy (mainly S-1) in patients with surgically resected pancreatic cancer. Materials and MethodsPatient selection. Between August 2013 and March 2016, patients with pancreatic cancer were consecutively enrolled in this study. During this period, patients with several types of cancer received the WT1-DC vaccine at the Center for Advanced Cell Therapy in Shinshu University Hospital (26). We selected those with pancreatic cancer who underwent resection after initial diagnosis and then received chemotherapy. We excluded patients who received chemotherapy before surgery. Other eligibility criteria have been previously described (27)....

Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review)

“…Wilms' tumor 1 (WT1) peptide-based vaccination combined with the adjuvant drug OK-432 administered to pediatric patients with a solid tumor has been demonstrated to be safe for these children ( 188 ). Furthermore, WT1-pulsed dendritic cell vaccine has been used to treat patients with surgically resected pancreatic cancer under a phase I study ( 189 ). A modified 9-mer WT1 peptide vaccine was also used in patients with gynecological cancer for inducing myeloid dendritic cells, and was demonstrated to be associated with cytotoxic T-cell activation ( 190 ).…”

Therapeutic Cancer Vaccination with Ex Vivo RNA-Transfected Dendritic Cells—An Update

“…Adding DC vaccination to any of the standard therapies seems reasonable, since there is sound evidence that these standard regimens will enhance the T-cell induction by vaccination so that an enhanced clinical effect is possible, and a negative impact of the DC vaccine regarding clinical benefit of the standard therapy is unlikely. Importantly, there is no evidence for significant enhancement of undesired side effects as cancer vaccines including DC vaccines have been used without unexpected or clearly enhanced toxicity problems in man together with chemotherapy [121][122][123][124], as well as immune checkpoint blockade (ICB) [43,81,[125][126][127][128]. With respect to combination with checkpoint blockade, anti-PD-1 is a preferred backbone for combinations with small molecules and immune stimulatory agents, but for resistant tumors (like uveal melanoma) double checkpoint blockade is used for triplet therapies as a novel concept.…”

From Genetic Alterations to Tumor Microenvironment: The Ariadne’s String in Pancreatic Cancer

“…DC-based vaccination has been shown to gemcitabine's therapeutic efficacy in the Panc02 poorly immunogenic murine tumor model [153]. Although preliminary clinical results with DC-based vaccination have shown tolerability and immunogenicity, clinical efficacy remains to be demonstrated [154,155].…”