Dendritic cell–based immunotherapy targeting Wilms’ tumor 1 in patients with recurrent malignant glioma

Sakai, Keiichi; Shimodaira, Shigetaka; Maejima, Shinya; Udagawa, Nobuyuki; Sakai, Kenji; Higuchi, Yumiko; Koya, Terutsugu; Ochiai, Takanaga; Koide, Masanori; Uehara, Satoshi; Nakamura, Midori; Sugiyama, Haruo; Yonemitsu, Yoshikazu; Okamoto, Masato; Hongo, Kazuhiro

doi:10.3171/2015.1.jns141554

Cited by 79 publications

(58 citation statements)

References 48 publications

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“…Cancer cells can evade immune recognition and destruction through loss or down-regulation of the expression of antigen-processing and antigen-presenting (27,28 molecules, such as class I and TAP (33,34). Therefore, the application of TAA peptide-specific CTL-based immunotherapy for cancer is thought to be difficult.…”

Section: Discussionmentioning

confidence: 99%

“…The WT1-DC vaccine was prepared according to a previously reported method (27,28 (27). WT1-DCs were suspended in a total volume of 1 ml of OK-432, and 1-4×10 7 WT1-DCs were injected at each time according to the number of DCs in each case.…”

Section: Methodsmentioning

confidence: 99%

“…The phenotypes of circulating T-cell populations were determined through fluorescence-activated cell sorting by measuring the total CD3 + population, CD4 + subpopulation, CD8 + subpopulation, activation markers HLA-DR on CD3 + cells, and other cell populations such as those of CD19-positive and CD56-positive cells. Enzyme-linked immunosorbent spot (ELISPOT) assays were performed using precoated human IFN-γ ELISPOT PLUS kits (Mabtech, Nacka Strand, Sweden) to examine WT1-specific interferon (IFN)-γ production by T-cells referred to as CTLs (27,28). The WT1 tetramer assay was performed only in patients who received the HLA-A*24:02-restricted mutant WT1 peptide.…”

Section: Evaluation Of Clinical Responsementioning

confidence: 99%

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

Yanagisawa

Koizumi

Koya

et al. 2018

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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)....

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Evaluation Of Clinical Responsementioning

confidence: 99%

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

Yanagisawa

Koizumi

Koya

et al. 2018

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“…Examples of recently studied tumor specific antigens include the use of an HLA restricted Wilms' tumor 1 epitope in recurrent high grade glioma patients 28 and a non-HLA restricted pancreatic bile salt protein in pancreatic adenocarcinoma. 29 A group in Japan pulsed autologous DC with a mix of WT-I and WT-II to expand the applicability of this approach and demonstrated increased EFS and OS in patients who had positive DTH skin testing to either antigen after administration.…”

Section: Antigen Selection and Loadingmentioning

confidence: 99%

Dendritic cell vaccines: A review of recent developments and their potential pediatric application

Elster

Krishnadas

Lucas

2016

Human Vaccines & Immunotherapeutics

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For many cancers the use of conventional chemotherapy has been maximized, and further intensification of chemotherapy generally results in excess toxicity with little long-term benefit for cure. Many tumors become resistant to chemotherapy, making the investigation of novel approaches such as immunotherapy of interest. Because the tumor microenvironment is known to promote immune tolerance and down regulate the body's natural defense mechanisms, modulating the immune system with the use of dendritic cell (DC) therapy is an attractive approach. Thousands of patients with diverse tumor types have been treated with DC vaccines. While antigen specific immune responses have been reported, the duration and magnitude of these responses are typically weak, and objective clinical responses have been limited. DC vaccine generation and administration is a multi-step process with opportunities for improvement in source of DC for vaccine, selection of target antigen, and boosting effector cell response via administration of vaccine adjuvant or concomitant pharmacologic immunomodulation. In this review we will discuss recent developments in each of these areas and highlight elements that could be moved into pediatric clinical trials.

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“…Five articles described for pancreatic cancer [19][20][21][22][23] , 2 for biliary tract cancer [24,25] , 1 for lung cancer [26] , 1 for ovarian cancer [27] , 1 for pediatric patient with relapsed leukemia [28] , 1 for gastric cancer [29] , 1 for malignant glioma [30] , and 1 for several types of advanced cancers treated with radiation therapy in combination with DC vaccine [31] . Here, we introduce the Vaccell's effects in pancreatic cancer patients in which the analysis has been progressed to most among these cases.…”

Section: Clinical Effects Of the Vaccell Mainly In Pancreatic Cancermentioning

confidence: 99%

Dendritic cell-based vaccine for pancreatic cancer in Japan

Okamoto

Kobayashi

Yonemitsu

et al. 2016

WJGPT

Self Cite

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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.

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Dendritic cell–based immunotherapy targeting Wilms’ tumor 1 in patients with recurrent malignant glioma

Cited by 79 publications

References 48 publications

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

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

Dendritic cell vaccines: A review of recent developments and their potential pediatric application

Dendritic cell-based vaccine for pancreatic cancer in Japan

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