A phase I study of combination therapy with WT1 peptide-pulsed dendritic cells and gemcitabine for advanced pancreatic and biliary tumors - Combination therapy with WT1 peptide-pulsed dendritic cells and gemcitabine

开始日期2010-09-01

申办/合作机构-

100 项与 WT1 peptide-loaded dendritic cell vaccine (Medinet) 相关的临床结果

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100 项与 WT1 peptide-loaded dendritic cell vaccine (Medinet) 相关的转化医学

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100 项与 WT1 peptide-loaded dendritic cell vaccine (Medinet) 相关的专利（医药）

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项与 WT1 peptide-loaded dendritic cell vaccine (Medinet) 相关的文献（医药）

2024-10-01·Journal for ImmunoTherapy of Cancer

Dendritic cells pulsed with multifunctional Wilms’ tumor 1 (WT1) peptides combined with multiagent chemotherapy modulate the tumor microenvironment and enable conversion surgery in pancreatic cancer

Article

作者: Shimodaira, Shigetaka ; Koido, Shigeo ; Yanagisawa, Hiroyuki ; Suka, Machi ; Sugiyama, Haruo ; Sato, Nobuhiro ; Tsukinaga, Shintaro ; Ito, Zensho ; Kan, Shin ; Bito, Tuuse ; Shimabuku, Masamori ; Uchiyama, Kan ; Ohkusa, Toshifumi ; Taguchi, Junichi ; Saruta, Masayuki ; Misawa, Takeyuki

BackgroundWe aimed to develop a chemoimmunotherapy regimen consisting of a novel Wilms’ tumor 1 (WT1) peptide-pulsed dendritic cell (WT1-DC) vaccine and multiagent chemotherapy and to investigate the safety, clinical outcomes, and WT1-specific immune responses of patients with unresectable advanced pancreatic ductal adenocarcinoma (UR-PDAC) who received this treatment.MethodsPatients with UR-PDAC with stage III disease (locally advanced (LA-PDAC; n=6)), stage IV disease (metastatic (M-PDAC; n=3)), or recurrent disease after surgery (n=1) were enrolled in this phase I study. The patients received one cycle of nab-paclitaxel plus gemcitabine alone followed by 15 doses of the WT1-DC vaccine independent of chemotherapy. The novel WT1 peptide cocktail was composed of a multifunctional helper peptide specific for major histocompatibility complex class II, human leukocyte antigen (HLA)-A*02:01, or HLA-A*02:06 and a killer peptide specific for HLA-A*24:02.ResultsThe chemoimmunotherapy regimen was well tolerated. In the nine patients for whom a prognostic analysis was feasible, the clinical outcomes of long-term WT1 peptide-specific delayed-type hypersensitivity (WT1-DTH)-positive patients (n=4) were significantly superior to those of short-term WT1-DTH-positive patients (n=5). During chemoimmunotherapy, eight patients were deemed eligible for conversion surgery and underwent R0 resection (four patients with LA-PDAC, one patient with M-PDAC, and one recurrence) or R1 resection (one patient with M-PDAC), and one patient with LA-PDAC was determined to be unresectable. Long-term WT1-DTH positivity was observed in three of the four patients with R0-resected LA-PDAC. These three patients exhibited notable infiltration of T cells and programmed cell death protein-1+ cells within the pancreatic tumor microenvironment (TME). All patients with long-term WT1-DTH positivity were alive for at least 4.5 years after starting therapy. In patients with long-term WT1-DTH positivity, the percentage of WT1-specific circulating CD4+ or CD8+ T cells that produced IFN-γ or TNF-α was significantly greater than that in patients with short-term WT1-DTH positivity after two vaccinations. Moreover, after 12 vaccinations, the percentages of both circulating regulatory T cells and myeloid-derived suppressor cells were significantly lower in patients with long-term WT1-DTH-positive PDAC than in short-term WT1-DTH-positive patients.ConclusionsPotent activation of WT1-specific immune responses through a combination chemoimmunotherapy regimen including the WT1-DC vaccine in patients with UR-PDAC may modulate the TME and enable conversion surgery, resulting in clinical benefits (Online supplemental file 1).Trial registration numberjRCTc030190195.

2021-12-01·Therapeutic Apheresis and Dialysis4区 · 医学

Predictive factors of poor blood collecting flow during leukocyte apheresis for cellular therapy

4区 · 医学

Article

作者: Shimodaira, Shigetaka ; Konno, Saori ; Yanagisawa, Ryu ; Motoki, Noriko

AbstractLeukocyte apheresis is necessary in various cellular therapies. However, maintenance of a stable flow rate during leukocyte apheresis is often difficult, even in patients or donors without major problems. Despite this, predictive methods and evidence regarding the reality of the situation are limited. We conducted a retrospective analysis involving adult patients who required leukocyte apheresis for the treatment of neoplasms using WT1‐pulsed dendritic cell vaccine. Monocytes were separated from apheresis products to obtain dendritic cells. All the patients were pre‐evaluated based on laboratory and chest X‐ray findings and subjected to an identical apheresis procedure. The occurrence of poor blood collecting flow during leukocyte apheresis was monitored, and the frequency, clinical information, and associated risk factors were analyzed. Among 160 cases, poor blood collecting flow was observed in 53 cases (33.1%) in a median time of 54 min (range, 2–127 min) post‐initiation of leukocyte apheresis. Owing to difficulty in obtaining higher collecting flow, a longer procedure time was required, and in some cases, the scheduled apheresis cycles could not be completed. Consequently, the number of harvested monocytes was low. Multivariable analysis indicated that female patients have an increased risk of poor inlet flow rate. Furthermore, prolonged QT dispersion (QTD) calculated using Bazett's formula was found to be a risk factor. Although the patients did not present any major problems during leukocyte apheresis, poor blood collecting flow was observed in some cases. Sex and pre‐evaluated QTD might be useful predictors for these cases; however, further prospective evaluation is necessary.

2018-03-28·Anticancer Research4区 · 医学

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

4区 · 医学

Article

作者: Koizumi, Tomonobu ; Koya, Terutsugu ; Yanagisawa, Ryu ; Shimodaira, Shigetaka ; Nagai, Kazuhiro ; Koido, Shigeo ; Okamoto, Masato ; Sano, Kenji ; Sugiyama, Haruo ; Kobayashi, Masanori

BACKGROUND/AIMWilms' 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 with chemotherapy in patients with surgically resected pancreatic cancer.PATIENTS AND METHODSEight patients with resectable pancreatic cancer undergoing surgery either combined with S-1 or S-1 plus gemcitabine therapy were enrolled. Immunohistochemical analysis of WT1 was performed in 34 cases of pancreatic cancer.RESULTSNo serious side-effects were observed, except grade I fever in five and grade I reactions at the injection site in all patients. WT1-specific cytotoxic T-lymphocytes were detected in seven patients, and WT1 and human leukocyte antigen class I antigens were positive in all 34 cases.CONCLUSIONOur study clarified the safety and potential acquisition of immunity after vaccination targeting WT1. Further efficacy of WT1-DC vaccine to improve prognosis would be determined by a prospective clinical trial for resectable pancreatic cancer.

100 项与 WT1 peptide-loaded dendritic cell vaccine (Medinet) 相关的药物交易

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